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  • 1985-1989  (118.329)
  • 1860-1869
  • 1850-1859
  • 1840-1849
  • 1985  (118.329)
Materialart
Erscheinungszeitraum
Jahr
  • 1
    Buch
    Buch
    Wien [u.a.] :Springer, ; 1.1977 - 16.2003; damit Ersch. eingest.
    Titel: Computing : archives for informatics and numerical computation; Supplementum
    Verlag: Wien [u.a.] :Springer,
    Erscheinungsjahr: 1977-2003
    Erscheinungsverlauf: 1.1977 - 16.2003; damit Ersch. eingest.
    Materialart: Buch
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Zeitschrift/Serie
    Zeitschrift/Serie
    New York, NY :ACM, ; 1.1969 - 7.1975/76; N.S. 1.1976 - 21.2001,1; damit Ersch. eingest.
    Titel: SIGBIO newsletter /
    Autor: Association for Computing Machinery / Special Interest Group on Biomedical Computing
    Verlag: New York, NY :ACM,
    Erscheinungsjahr: 1969-2001
    Erscheinungsverlauf: 1.1969 - 7.1975/76; N.S. 1.1976 - 21.2001,1; damit Ersch. eingest.
    ISSN: 0163-5697
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Paralleltitel: Internetausg. ---〉:Biomedical computing
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  • 3
    Zeitschrift/Serie
    Zeitschrift/Serie
    New York, NY :North-Holland, ; 1.1984 - 46.2000
    Titel: ¬The¬ journal of logic programming
    Verlag: New York, NY :North-Holland,
    Erscheinungsjahr: 1984-2000
    Erscheinungsverlauf: 1.1984 - 46.2000
    ISSN: 0743-1066
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Nachfolgender Titel: Forts. ---〉:¬The¬ journal of logic and algebraic programming
    Paralleltitel: Internetausg. ---〉:¬The¬ journal of logic and algebraic programming
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Buch
    Buch
    New York, NY :ACM, ; Nachgewiesen 2.1971 - 20.1999,4; damit Ersch. eingest.
    Titel: Computer personnel : a quarterly publ. of the Special Interest Group on Computer Personnel Research, SIGCPR
    Verlag: New York, NY :ACM,
    Erscheinungsjahr: 1971-1999
    Erscheinungsverlauf: Nachgewiesen 2.1971 - 20.1999,4; damit Ersch. eingest.
    ISSN: 0160-2497
    Materialart: Buch
    Paralleltitel: Internetausg. ---〉:Computer personnel
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    Zeitschrift/Serie
    Zeitschrift/Serie
    New York, NY :ACM, ; 4.1969 - 33.1998,2; damit Ersch. eingest
    Titel: SIGNUM newsletter
    Autor: Association for Computing Machinery / Special Interest Group on Numerical Mathematics
    Verlag: New York, NY :ACM,
    Erscheinungsjahr: 1969-1998
    Erscheinungsverlauf: 4.1969 - 33.1998,2; damit Ersch. eingest
    ISSN: 0163-5778
    Materialart: Zeitschrift/Serie
    Vorheriger Titel: Vorg. ---〉:Association for Computing Machinery / Special Interest Committee on Numerical Mathematics: SICNUM newsletter
    Suppl.: 16,3=3,2 von:Association for Computing Machinery / Technical Committee on Fortran: FORTEC forum
    Paralleltitel: Internetausg. ---〉:Numerical mathematics
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 6
    Zeitschrift/Serie
    Zeitschrift/Serie
    San Francisco, Calif. :Miller Freeman, ; 1.1983 - 16.1998,3
    Titel: Unix review : the publication for the Unix community
    Verlag: San Francisco, Calif. :Miller Freeman,
    Erscheinungsjahr: 1983-1998
    Erscheinungsverlauf: 1.1983 - 16.1998,3
    ISSN: 0742-3136
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Nachfolgender Titel: Forts. ---〉:Unix review's performance computing
    Paralleltitel: Internetausg. ---〉:Unix review.com
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  • 7
    Zeitschrift/Serie
    Zeitschrift/Serie
    Amsterdam [u.a.] :Elsevier [u.a.], ; 9.1985 - 30.1998
    Titel: Computer networks and ISDN systems : the international journal of computer and telecommunications networking
    Verlag: Amsterdam [u.a.] :Elsevier [u.a.],
    Erscheinungsjahr: 1985-1998
    Erscheinungsverlauf: 9.1985 - 30.1998
    ISSN: 0169-7552 , 0376-5075
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Nachfolgender Titel: Vorg. u. Forts. ---〉:Computer networks
    Anmerkung: Computer networks for research in Europe
    Suppl.: In 14,1=15 von:Networkshop: Conference report
    Suppl.: 16,1/2=4; 17,4/5=5 von:European Networkshop: European Networkshop
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  • 8
    Zeitschrift/Serie
    Zeitschrift/Serie
    Amsterdam :Amsterdam Universities Computing Centre, ; Nr. 1.1984 - 69.1997; damit Ersch. eingest.
    Titel: Supercomputer : bimonthly magazine on supercomputing in the Netherlands
    Verlag: Amsterdam :Amsterdam Universities Computing Centre,
    Erscheinungsjahr: 1984-1997
    Erscheinungsverlauf: Nr. 1.1984 - 69.1997; damit Ersch. eingest.
    ISSN: 0168-7875
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Anmerkung: Teils auch mit Jg.-Zählung
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  • 9
    Buch
    Buch
    Bergheim :DATACOM-Zeitschriften-Verl., | Köln Müller -1993,9 ; 11.1973 - 14.1976; 19.1981 - 20.1982; 1983 - 1994; 32.1995 - 34.1997,10
    Titel: Online : erfolgreiches Informationsmanagement, ADI-Nachrichten, ÖVD ; Organ d. ADI - Anwenderverband Deutscher Informationsverarbeiter e.V
    Beteiligte Person(en): Anwenderverband Deutscher Informationsverarbeiter
    Verlag: Bergheim :DATACOM-Zeitschriften-Verl., , Köln Müller -1993,9
    Erscheinungsjahr: 1973-1997
    Erscheinungsverlauf: 11.1973 - 14.1976; 19.1981 - 20.1982; 1983 - 1994; 32.1995 - 34.1997,10
    ISSN: 0340-1545 , 0179-6623 , 0342-9393
    Materialart: Buch
    Sprache: Unbestimmte Sprache
    Vorheriger Titel: Vorg. ---〉:Zeitschrift für Datenverarbeitung
    Nachfolgender Titel: 15.1977 - 18.1980 ---〉:ADL-Verband für Informationsverarbeitung: ADL-Nachrichten, Online
    Nachfolgender Titel: Aufgeg. in ---〉:Information week
    Anmerkung: Später ohne Zählung
    Suppl.: Beil. ---〉:Drucker spezial
    Suppl.: Beil. ---〉:Online / special
    Suppl.: Darin ---〉:Anwenderverband Deutscher Informationsverarbeiter: ADI-Nachrichten, ÖVD
    Suppl.: Beil. ---〉:Pro info
    Suppl.: Beil. ---〉:Online-Info
    Suppl.: 1996 darin ---〉:Datacom-Special
    Paralleltitel: 19.1981 auch in ---〉:Öffentliche Verwaltung und Datenverarbeitung
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  • 10
    Zeitschrift/Serie
    Zeitschrift/Serie
    Minneapolis, Minn. :Cray Research, Inc., ; Nachgewiesen 6.1984 - 18.1996,2; damit Ersch. eingest.
    Titel: Cray channels : a Cray Research, Inc. publication
    Beteiligte Person(en): Cray Research, Inc. 〈Mendota Heights, Minn.〉
    Verlag: Minneapolis, Minn. :Cray Research, Inc.,
    Erscheinungsjahr: 1984-1996
    Erscheinungsverlauf: Nachgewiesen 6.1984 - 18.1996,2; damit Ersch. eingest.
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 11
    Zeitschrift/Serie
    Zeitschrift/Serie
    München :Hanser, ; 1.1983 - 14.1996,6
    Titel: Unix mail : Europas erster Informationsdienst für Unix-Hersteller und -Anwender
    Verlag: München :Hanser,
    Erscheinungsjahr: 1983-1996
    Erscheinungsverlauf: 1.1983 - 14.1996,6
    ISSN: 0176-8654
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Nachfolgender Titel: Forts. ---〉:¬Die¬ blauen Blätter
    Paralleltitel: CD-ROM-Ausg. ---〉:Unix mail, die blauen Blätter
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  • 12
    Titel: Nachrichtentechnische Zeitschrift : NTZ ; Zeitschrift für Informationstechnik u. Telekommunikation ; Organ der Nachrichtentechnischen Gesellschaft im VDE
    Beteiligte Person(en): Nachrichtentechnische Gesellschaft / Fachausschuß Informationsverarbeitung
    Verlag: Berlin :VDE-Verl.,
    Erscheinungsjahr: 1955-1995
    Erscheinungsverlauf: 8.1955,10 - 40.1987,2; 40.1987,6 - 48.1995,2
    ISSN: 0027-707X
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Vorheriger Titel: Vorg. ---〉:Fernmeldetechnische Zeitschrift
    Nachfolgender Titel: 40.1987,3-5 u. Forts. ---〉:NTZ
    Anmerkung: Mikro-Elektronik
    Suppl.: Beih. ---〉:Nachrichtentechnische Fachberichte
    Suppl.: Index 1/10=11 von:Nachrichtentechnische Fachberichte
    Paralleltitel: CD-ROM-Ausg. 1994 - 1995 ---〉:Elektronisches Zeitschriftenarchiv
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  • 13
    Zeitschrift/Serie
    Zeitschrift/Serie
    Stuttgart :IBM, ; 22.1972,Apr. - 45.1995 = Nr. 210-323; damit Ersch. eingest.
    Titel: IBM-Nachrichten /
    Autor: IBM Deutschland GmbH 〈Stuttgart〉
    Verlag: Stuttgart :IBM,
    Erscheinungsjahr: 1972-1995
    Erscheinungsverlauf: 22.1972,Apr. - 45.1995 = Nr. 210-323; damit Ersch. eingest.
    ISSN: 0018-8662
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Vorheriger Titel: Vorg. ---〉:Internationale Büro-Maschinen-Gesellschaft Deutschland 〈Sindelfingen〉: IBM-Nachrichten
    Suppl.: Beil. ---〉:Hollerith-Mitteilungen
    Paralleltitel: CD-ROM-Ausg. ---〉:IBM Deutschland GmbH 〈Stuttgart〉: IBM-Nachrichten
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  • 14
    Zeitschrift/Serie
    Zeitschrift/Serie
    Oxford [u.a.] :Pergamon Press, ; 1.1960 - 19.1995
    Titel: Annual review in automatic programming
    Verlag: Oxford [u.a.] :Pergamon Press,
    Erscheinungsjahr: 1960-1995
    Erscheinungsverlauf: 1.1960 - 19.1995
    ISSN: 0066-4138
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Nachfolgender Titel: Forts. ---〉:Annual reviews in control
    Suppl.: 1=3; 2=6, 3=11, 4=12; 5=13,2 von:International tracts in computer science and technology and their application
    Suppl.: 8=7; 9,2/3=8; 10=10; 11=11; 13,1=13; 14,1=15 von:Real time programming
    Suppl.: 12,1-12,2=2 von:Systems analysis and simulation
    Suppl.: 13,2=5 von:Control applications of nonlinear programming and optimization
    Paralleltitel: Internetausg. ---〉:Annual reviews in control
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  • 15
    Zeitschrift/Serie
    Zeitschrift/Serie
    Heidelberg :Physica-Verl., ; 16.1972 - 42.1995
    Titel: Zeitschrift für Operations-Research : ZOR ; mathematical methods of operations research
    Verlag: Heidelberg :Physica-Verl.,
    Erscheinungsjahr: 1972-1995
    Erscheinungsverlauf: 16.1972 - 42.1995
    ISSN: 0340-9422
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Vorheriger Titel: Vorg. ---〉:Ablauf- und Planungsforschung
    Nachfolgender Titel: Forts. ---〉:Mathematical methods of operations research
    Anmerkung: Ser. A, Theorie = H. 1,3,5,7 d. Jg.; Ser. B, Praxis = H. 2,4,6,8 d. Jg. , Deutsche Gesellschaft für Operations-Research
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  • 16
    Zeitschrift/Serie
    Zeitschrift/Serie
    New York, NY :ACM, ; 2.1971/72 - 16.1985; 19.1988 - 26.1995; damit Ersch. eingest.
    Titel: SIGMICRO newsletter : a quarterly publ. of the Special Interest Group on Microprogramming
    Autor: Association for Computing Machinery / Special Interest Group on Microprogramming
    Verlag: New York, NY :ACM,
    Erscheinungsjahr: 1971-1995
    Erscheinungsverlauf: 2.1971/72 - 16.1985; 19.1988 - 26.1995; damit Ersch. eingest.
    ISSN: 0163-5751 , 1050-916X
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Vorheriger Titel: Vorg. ---〉:Association for Computing Machinery / Special Interest Committee on Microprocessing: SICMICRO newsletter
    Nachfolgender Titel: 17.1986 - 18.1987 ---〉:Association for Computing Machinery / Special Interest Group on Microprogramming: SIGMICRO TCMICRO newsletter
    Suppl.: Beil. ---〉:Microprogramming bibliography
    Suppl.: 9,4=11; 12,4=14; 13,4=15 von:Micro
    Suppl.: 20,3=22 von:International Workshop on Microprogramming and Microarchitecture: Annual International Workshop on Microprogramming and Microarchitecture
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  • 17
    Titel: Data-base 〈New York,NY〉 : db ; a quarterly publication of the Special Interest Group on Business Information Technology of the Association for Computing Machinery
    Beteiligte Person(en): Association for Computing Machinery / Special Interest Group on Business Data Processing , Association for Computing Machinery / Special Interest Group on Business Information Technology
    Verlag: New York, NY,
    Erscheinungsjahr: 1971-1994
    Erscheinungsverlauf: 3.1971 - 25.1994
    ISSN: 0095-0033
    Materialart: Buch
    Vorheriger Titel: Vorg. ---〉 SIGBDP news-letter
    Nachfolgender Titel: Forts. ---〉:¬The¬ data-base for advances in information systems
    Suppl.: Einzelne Bd. zugl. Bd. von:Association for Computing Machinery / Special Interest Group on Management of Data: SIGMOD record
    Suppl.: 12,4u.13,1=2 von:Data-base directions
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  • 18
    Zeitschrift/Serie
    Zeitschrift/Serie
    München :Franzis-Verl., ; 1981 - 1994,6
    Titel: MC 〈München〉 : Computerpraxis für technische Anwender
    Verlag: München :Franzis-Verl.,
    Erscheinungsjahr: 1981-1994
    Erscheinungsverlauf: 1981 - 1994,6
    ISSN: 0720-4442 , 0941-777X , 0943-5409
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Nachfolgender Titel: Aufgeg. in ---〉:DOS international
    Anmerkung: Auch mit fehlerhafter Jg.-Zählung im Impressum
    Suppl.: 1992 Sonderh. ---〉:WINbox
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  • 19
    Zeitschrift/Serie
    Zeitschrift/Serie
    London [u.a.], ; 1.1969 - 39.1993
    Titel: International journal of man machine studies
    Verlag: London [u.a.],
    Erscheinungsjahr: 1969-1993
    Erscheinungsverlauf: 1.1969 - 39.1993
    ISSN: 0020-7373
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Nachfolgender Titel: Forts. ---〉:International journal of human - computer studies
    Anmerkung: Index 1/4.1969/72 in: 4.1972
    Suppl.: 10,3=5 von:Man Computer Communications Conference: Proceedings
    Paralleltitel: Internetausg. ---〉:International journal of man machine studies
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  • 20
    Titel: SIGSMALL - PC notes : a publication of the Special Interest Group on Small and Personal Computing Systems and Applications, Association for Computing Machinery
    Autor: Association for Computing Machinery / Special Interest Group on Small and Personal Computing Systems and Applications
    Verlag: New York, NY :ACM,
    Erscheinungsjahr: 1984-1993
    Erscheinungsverlauf: 10.1984,4 - 19.1993/94,2(1993)
    ISSN: 0893-2875
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Vorheriger Titel: Vorg. ---〉:Association for Computing Machinery / Special Interest Group on Small Computing Systems and Applications: SIGSMALL newsletter
    Nachfolgender Titel: Forts. ---〉:Association for Computing Machinery / Special Interest Group on Individual Computing Environments: SIGICE bulletin
    Anmerkung: Zählung von "SIGSMALL newsletter" übernommen
    Paralleltitel: Internetausg. ---〉:Association for Computing Machinery / Special Interest Group on Small and Personal Computing Systems and Applications: ACM SIGSMALL - PC notes
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  • 21
    Titel: SIGACT news : publ. by the ACM Special Interest Group on Automata and Computability Theory
    Autor: Association for Computing Machinery / Special Interest Group on Automata and Computability Theory
    Beteiligte Person(en): Association for Computing Machinery / Special Interest Committee on Automata and Computability Theory
    Verlag: New York, NY :ACM,
    Erscheinungsjahr: 1969-1992
    Erscheinungsverlauf: 1.1969 - 23.1992,2 = Nr. 1-83
    ISSN: 0163-5700
    Materialart: Zeitschrift/Serie
    Nachfolgender Titel: Forts. ---〉:Association for Computing Machinery / Special Interest Group on Algorithms and Computation Theory: SIGACT news
    Suppl.: In 12.1980,2 Index 1/12.1969/80 von ---〉:Symposium on Theory of Computing: Conference record of the ... annual ACM Symposium on Theory of Computing
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  • 22
    Titel: SIGPLAN notices : a monthly publication of the Special Interest Group on Programming Languages of the Association for Computing Machinery
    Autor: Association for Computing Machinery / Special Interest Group on Programming Languages
    Verlag: New York, NY :ACM,
    Erscheinungsjahr: 1966-1991
    Erscheinungsverlauf: 1.1966 - 26.1991,9u.11
    ISSN: 0362-1340
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Nachfolgender Titel: 26.1991,10 u. Forts. ---〉:Association for Computing Machinery / Special Interest Group on Programming Languages: ACM SIGPLAN notices
    Suppl.: 6,2=1971 von:Symposium on Data Structures in Programming Languages: Proceedings of a Symposium on Data Structures in Programming Languages
    Suppl.: 17,4=10,2; 22,10=15,5; 24,spec.iss.=17,2; 26,4=19,2 von:Computer architecture news
    Suppl.: 21,10=1986 von:Workshop on Object Oriented Programming: Transcript
    Suppl.: 11,6=10,1 von:Computer graphics
    Suppl.: 16,6=2,1/2 von:Association for Computing Machinery / Special Interest Group on Office Automation: SIGOA newsletter
    Suppl.: 14,8=1979; 17,6=1982; 19,6=1984; 21,7=1986 von:Symposium on Compiler Construction: Proceedings of the SIGPLAN Symposium on Compiler Construction
    Suppl.: 20,7=1985 von:Symposium on Language Issues in Programming Environments: Proceedings of the ACM SIGPLAN ... Symposium on Language Issues in Programming Environments
    Suppl.: 19,5=1; 22,1=2; 24,2=3 von:Software Engineering Symposium on Practical Software Development Environments: Proceedings of the ACM SIGSOFT SIGPLAN Software Engineering Symposium on Practical Software Development Environments
    Suppl.: 22,10=2; 24,spec.iss.=3 von:International Conference on Architectural Support for Programming Languages and Operating Systems: Proceedings
    Suppl.: 23,7=1988; 24,7=1989; 25,6=1990 von:Conference on Programming Language Design and Implementation: Proceedings of the SIGPLAN ... Conference on Programming Language Design and Implementation
    Suppl.: 21,11=1; 22,12=2; 23,11=3; 24,10=4 von:OOPSLA: Conference proceedings
    Suppl.: 22,10=21,4; 24,spec.iss.=23,spec.iss.; 26,4=25,spec.iss. von:Operating systems review
    Suppl.: 17,4=1982 von:Symposium on Architectural Support for Programming Languages and Operating Systems: Proceedings
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  • 23
    Titel: SIGART newsletter : a bimonthly publ. of the ACM Special Interest Group on Artificial Intelligence
    Autor: Association for Computing Machinery / Special Interest Group on Artificial Intelligence
    Verlag: New York, NY :ACM,
    Erscheinungsjahr: 1969-1989
    Erscheinungsverlauf: Nachgewiesen Nr. 15.1969 - 110.1989
    ISSN: 0163-5719
    Materialart: Zeitschrift/Serie
    Nachfolgender Titel: Forts. ---〉:Association for Computing Machinery / Special Interest Group on Artificial Intelligence: SIGART bulletin
    Suppl.: 73=1; 80=2 von:Workshop on Distributed AI: Report on the Workshop on Distributed AI
    Suppl.: 84=3 von:Workshop on Distributed Artificial Intelligence: Report on the ... Annual Workshop on Distributed Artificial Intelligence
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  • 24
    Zeitschrift/Serie
    Zeitschrift/Serie
    Braunschweig ; Wiesbaden :Vieweg, ; 13.1971 - 31.1989
    Titel: Angewandte Informatik : Applied informatics
    Verlag: Braunschweig ; Wiesbaden :Vieweg,
    Erscheinungsjahr: 1971-1989
    Erscheinungsverlauf: 13.1971 - 31.1989
    ISSN: 0013-5704
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Vorheriger Titel: Vorg. ---〉:Elektronische Datenverarbeitung
    Suppl.: Beil. CAK
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  • 25
    Zeitschrift/Serie
    Zeitschrift/Serie
    Amsterdam :North-Holland Publ. Co., ; 1.1974 - 31.1987.
    Titel: Mathematical programming /; Study
    Beteiligte Person(en): Mathematical Programming Society
    Verlag: Amsterdam :North-Holland Publ. Co.,
    Erscheinungsjahr: 1974-1987
    Erscheinungsverlauf: 1.1974 - 31.1987.
    ISSN: 0303-3929
    Materialart: Zeitschrift/Serie
    Nachfolgender Titel: :Mathematical programming / B
    Suppl.: 13:Conference on Combinatorial Optimization: Conference on Combinatorial Optimization
    Suppl.: 27-28:Stochastic programming
    Suppl.: 22:Mathematical programming at Oberwolfach
    Suppl.: :Combinatorial optimization
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  • 26
    Zeitschrift/Serie
    Zeitschrift/Serie
    Amsterdam :North-Holland Publ., ; 1.1971 - 39.1987
    Titel: Mathematical programming /
    Beteiligte Person(en): Mathematical Programming Society
    Verlag: Amsterdam :North-Holland Publ.,
    Erscheinungsjahr: 1971-1987
    Erscheinungsverlauf: 1.1971 - 39.1987
    ISSN: 0025-5610
    Materialart: Zeitschrift/Serie
    Anmerkung: Teils ohne Unterreihenbez.
    Suppl.: 1,1-3=7; 4-5=8 von:International Mathematical Programming Symposium: Proceedings of the ... International Mathematical Programming Symposium
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  • 27
    Zeitschrift/Serie
    Zeitschrift/Serie
    München ; Wien :Hanser, ; 1.1978 - 9.1986,2
    Titel: ¬Das¬ Rechenzentrum : Fachzeitschrift für d. Betrieb von DV-Systemen in Wirtschaft u. Verwaltung, Wissenschaft, Medizin u. Technik
    Verlag: München ; Wien :Hanser,
    Erscheinungsjahr: 1978-1986
    Erscheinungsverlauf: 1.1978 - 9.1986,2
    ISSN: 0343-317X
    Materialart: Zeitschrift/Serie
    Sprache: Unbestimmte Sprache
    Nachfolgender Titel: Forts. ---〉:Praxis der Informationsverarbeitung und Kommunikation
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  • 28
    Zeitschrift/Serie
    Zeitschrift/Serie
    New York, NY [u.a.] :Academ. Pr., ; 1.1957/58 - 71.1986
    Titel: Information and control
    Verlag: New York, NY [u.a.] :Academ. Pr.,
    Erscheinungsjahr: 1957-1986
    Erscheinungsverlauf: 1.1957/58 - 71.1986
    ISSN: 0019-9958
    Materialart: Zeitschrift/Serie
    Nachfolgender Titel: Forts. ---〉:Information and computation
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  • 29
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Presynaptic actions of kainic acid have been tested on uptake and release mechanisms in synaptosome-enriched preparations from rat hippocampus and goldfish brain. Kainic acid increased in a Ca2+-dependent way the basal release of endogenous glutamate and aspartate from both synaptosomal preparations, with the maximum effect (40–80%) being reached at the highest concentration tested (1 mM). In addition, kainic acid potentiated, in an additive or synergic way, the release excitatory amino acids stimulated by high K+ concentrations. Kainic acid at 1 mM showed a completely opposite effect on the release of exogenously accumulated D-[3H]aspartate. The drug, in fact, caused a marked inhibition of both the basal and the high K+-stimulated release. Kainic acid at 0.1 mM had no clear-cut effect, whereas at 0.01 mM it caused a small stimulation of the basal release. The present results suggest that kainic acid differentially affects two neurotransmitter pools that are not readily miscible in the synaptic terminals. The release from an endogenous, possibly vesiculate, pool of excitatory amino acids is stimulated, whereas the release from an exogenously accumulated, possibly cytoplasmic and carrier-mediated, pool is inhibited or slightly stimulated, depending on the external concentration of kainic acid. Kainic acid, in addition, strongly inhibits the high-affinity uptake of L-glutamate and D-aspartate in synaptic terminals. All these effects appear specific for excitatory amino acids, making it likely that they are mediated through specific recognition sites present on the membranes of glutamatergic and aspartatergic terminals. The relevance of the present findings to the mechanism of excitotoxicity of kainic acid is discussed.
    Materialart: Digitale Medien
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  • 30
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Leptinotoxin-h (LPTx), a neurotoxin (otherwise designated β-leptinotarsin-h) known to stimulate the release of neurotransmitters from synapses, was purified from the hemolymph of the potato beetle, Leptinotarsa haldemani, by a simplification of the procedure originally developed by Crosland et al. [Biochemistry23, 734–741, (1984)]. Highly and partially purified preparations of the toxin were applied to guinea pig synaptosomes and neurosecretory (PC12) cells. When applied in a Ca2+-containing Ringer medium, at concentrations in the 10−11-10−10M range, the toxin induced: (a) rapid depolarization of the plasma membrane, which was not inhibited by organic blockers of voltage-dependent Na+ and Ca2+ channels (tetrodotoxin or verapamil); (b) large 45Ca influx: and (c) increased free cytosolic Ca2+ concentration. These latter two effects were unaffected by verapamil. In Ca2+-free media the effects of the toxin were different in the two systems investigated. In synaptosomes, depolarization was still observed, even if the toxin concentrations needed were higher (10X) than those effective in the complete medium. In contrast, in PC12 cells no effect of the toxin on membrane potential was observed. Binding of LPTx to its cellular targets could not be investigated directly because the toxin was inactivated by the procedures used for its labeling. Indirect evidence suggested however that Ca2+ is necessary for toxin binding to PC12 cells. Interaction of LPTx with air/water interfaces, as well as with cholesterol/phospholipid mono- and bilayer membranes was investigated. The results indicate that the toxin has affinity for hydrophobic surfaces, but lacks the capacity to insert across membranes unless transpositive voltage is applied. Our results are inconsistent with the previous conclusion of Crosland et al. (1984), who suggested opening of the Ca2+ channel as the mechanism of action of LPTx. The effects of the toxin resemble those of α-latrotoxin (α-LTx) of the black widow spider venom, and therefore the two toxins might act by similar mechanisms. However, the sites recognized by the two toxins might be different, because LPTx does not inhibit α-LTx binding.
    Materialart: Digitale Medien
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  • 31
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Cultured NCB-20 hybrid cells express adenylate cyclase-coupled receptors for 5-hydroxytryptamine (5-HT) that correspond biochemically and pharmacologically to 5-HT1 receptors in rodent brain membrane preparations, apart from a much-reduced affinity for 5-HT (160 nM compared to 〈 5 nM in brain). Since NCB-20 cells also differ from rodent brain both qualitatively and quantitatively in their ganglioside composition, the effects of exogenously added gangliosides on the affinity of the 5-HT1 receptor for 5-HT were tested. Both GM1 ganglioside (the cholera toxin receptor) and tetrasialoganglioside GQ1b produced a 10-fold increase in receptor affinity for [3H]5-HT, measured by binding studies. All gangliosides, at submicromolar concentrations, resulted in significantly reduced EC50 values for 5-HT-mediated elevation of intracellular cyclic AMP levels. GQ1b had the capacity to most dramatically enhance the potency of 5-HT in mediating increases in cyclic AMP levels. Gangliosides had no effect on the potency of DADLE or 3,4-dihydroxyphenylethylamine (dopamine)-mediated depression of cyclic AMP levels, suggesting some specificity for 5-HT. Our data are interpreted as implying a specific role for polysialogangliosides in modulating the affinity of the 5-HT1 receptor and the coupling of the 5-HT1 receptor-guanine nucleotide binding protein adenylate cyclase complex.
    Materialart: Digitale Medien
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  • 32
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Barbiturates in pharmacologically relevant concentrations inhibit binding of (R)-N6-phenylisopropyl[3H]adenosine ([3H]PIA) to solubilized A1 adenosine receptors in a concentration-dependent, stereospecific, and competitive manner. Ki values are similar to those obtained for membrane-bound receptors and are 31 μM for (±)-5-(1,3-dimethyl)-5-ethylbarbituric acid [(±)-DMBB] and 89 μM for (±)-pentobarbital. Kinetic experiments demonstrate that barbiturates compete directly for the binding site of the receptor. The inhibition of rat striatal adenylate cyclase by unlabelled (R)-N6-phenyl-isopropyladenosine [(R)-PIA] is antagonized by barbiturates in the same concentrations that inhibit radioligand binding. The stimulation of adenylate cyclase via A2 adenosine receptors in membranes from N1E 115 neuroblastoma cells is antagonized only by 10–30 times higher concentrations of barbiturates. It is concluded that barbiturates are selective antagonists at the A1 receptor subtype. In analogy to the excitatory effects of methylxanthines it is suggested that A1 adenosine receptor antagonism may convey excitatory properties to barbiturates.
    Materialart: Digitale Medien
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  • 33
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: A possible alternative route for production of a small glutamate pool in brain is from proline or ornithine to 1-pyrroline-5-carboxylate (P5C) and thence to glutamate. The conversion from ornithine to P5C is catalyzed by ornithine δ-aminotransferase (OrnT) whereas that from proline is catalyzed by proline oxidase (PrO). The conversion of P5C to glutamate is catalyzed by 1-pyrroline-5-carboxylate dehydrogenase (PDH). Biochemical assays of PDH and PrO in various rat brain regions indicate no positive correlation between the two enzymes nor between either activity and high-affinity glutamate uptake or the regional distribution of OrnT. We have localized PDH and PrO histochemically by modifications of the Van Gelder [J. Neurochem.12, 231–237, (1965)] method for γ-aminobutyric acid (GABA) transaminase. The enzymes were found only in certain types of glial cells; the best stained were the Bergmann glial cells of the cerebellum but, for PDH, there was also good staining of astrocytes in the dentate area of the hippocampus. Since both these areas are believed to have heavy glutamate innervation and numerous GABA interneurons, these findings may reflect an alternative route of glutamate production in glial cells near some glutamate and/or GABA tracts but they do not support this as a possible route for glutamate formation in most brain regions. The findings do, however, provide further evidence for chemical specialization of glial cells.
    Materialart: Digitale Medien
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  • 34
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Elements of three neurotransmitter systems were investigated in morphologically undifferentiated human Y-79 retinoblastoma cells in suspension culture. Specific γ-aminobutyric acid (GABA) uptake, GABA binding, and glycine binding were absent from these cells, although the cells had been shown to exhibit an active uptake and release of [3H]glycine. Binding and competition studies using both α-and β-adrenergic ligands indicated the presence of a β-adrenergic receptor. This finding was confirmed by treatment of the cells with β-agonists in competition with a β-antagonist and with an α-antagonist; the level of cyclic AMP was competitively stimulated. Therefore, human Y-79 cells in suspension culture contain β-adrenergic receptors, and not glycinergic or GABAergic ones. Thus, the Y-79 cells may be of use in studying the factors involved in developmental regulation of neurotransmitter function.
    Materialart: Digitale Medien
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  • 35
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: (E)-β-Fluoromethylene-m-tyrosine (FMMT) is a dual-enzyme-activated inhibitor of monoamine oxidase (MAO). The compound is not an inhibitor per se but is decarboxylated by aromatic L-amino acid decarboxylase (AADC) to yield a potent enzyme-activated irreversible inhibitor of MAO, (E)-β-fluoromethylene-m-tyramine, which shows some selectivity for inhibition of MAO type A. Decarboxylation of FMMT was demonstrated in vitro using hog kidney AADC and in vivo in rats by the ability of α-monofluoromethyldopa (MFMD), a potent inhibitor of AADC, to prevent MAO inhibition produced by FMMT. In isolated synaptosomes. FMMT was decarboxylated by AADC, and, furthermore, the compound was actively transported into these isolated nerve endings. An active transport into the CNS has also been demonstrated in vivo by performing competition experiments with leucine. To demonstrate that FMMT is preferentially decarboxylated within monoamine nerves of the CNS, the nigrostriatal 3,4-dihydroxyphenylethylamine (dopamine) pathway of rats was unilaterally lesioned with 6-hydroxydopamine or infused with MFMD. Under these conditions, MAO inhibition produced by orally administered FMMT in the striatum ipsilateral to the lesion or infusion was markedly attenuated. Combination of FMMT with an inhibitor of extracerebral AADC, such as carbidopa, protected peripheral organs against the MAO inhibitory effects and concomitantly enhanced MAO inhibition in the CNS. Such combinations had a greatly reduced propensity to augment the cardiovascular effects of intraduodenally administered tyramine, when compared with FMMT given alone or with clorgyline, a selective inhibitor of MAO type A. The results obtained with FMMT suggest the possibility of achieving selective inhibition of MAO within monoamine nerves of the CNS and, further, suggest that combination of FMMT with an inhibitor of extracerebral AADC will reduce the propensity of this inhibitor to produce adverse interactions with tyramine.
    Materialart: Digitale Medien
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  • 36
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Somatostatin-like immunoreactivity (SLI) was purified from frog brain and retina, and the structure of the brain peptide was determined. Frog brain (101 g) and retinal (45 g) tissues were extracted with 3% acetic acid, yielding 9.6 and 0.44 nmol of SLI, respectively. SLI was further purified by chromatography on a somatostatin immunoaffinity column followed by sequential application to reverse-phase C-18 HPLC columns. The brain and retinal peptides, purified roughly 100,000-fold with net yields of 7.5 and 2.3%, respectively, appeared identical in the final steps of purification. The amino acid sequence of brain SLI, as determined by a gas-phase automated Edman degradation technique, was as follows: Ala-Gly (Cys)-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser- (Cys). Our data indicate that despite structural variations in somatostatins of other lower vertebrates, the amino acid sequence of frog brain and, by deduction, retinal SLI is identical to that of somatostatin tetradecapeptide. These findings support the physiological relevance of studies directed at elucidating the neurotransmitter function of somatostatin using the well-established models of frog brain and retina.
    Materialart: Digitale Medien
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  • 37
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Acetaldehyde and biogenic aldehydes were used as substrates to investigate the subcellular distribution of aldehyde dehydrogenase activity in autopsied human brain. With 10 μM acetaldehyde as substrate, over 50% of the total activity was found in the mitochondrial fraction and 38% was associated with the cytosol. However, with 4 μM 3,4-dihydroxyphenylacetaldehyde and 10 μM indoleacetaldehyde as substrates, 40–50% of the total activity was found in the soluble fraction, the mitochondrial fraction accounting for only 15–30% of the total activity. These data suggested the presence of distinct aldehyde dehydrogenase isozymes in the different compartments. The mitochondrial and cytosolic fractions were, therefore, subjected to salt fractionation and ion-exchange chromatography to purify further the isozymes present in both fractions. The kinetic data on the partially purified isozymes revealed the presence of a low Km isozyme in both the mitochondria and the cytosol, with Km values for acetaldehyde of 1.7 μM and 10.2 μM, respectively. However, the cytosolic isozyme exhibited lower Km values for the biogenic aldehydes. Both isozymes were activated by Mg2+ and Ca2+ in phosphate buffers (pH 7.4). Also, high Km isozymes were found in the mitochondria and in the microsomes.
    Materialart: Digitale Medien
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  • 38
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: We have correlated membrane structure and interactions in shiverer sciatic nerve myelin with its biochemical composition. Analysis of x-ray diffraction data from shiverer myelin swollen in water substantiates our previous localization of an electron density deficit in the cytoplasmic half of the membrane. The density loss correlates with the absence of the major myelin basic proteins and indicates that in normal myelin, the basic protein is localized to the cytoplasmic apposition. As in normal peripheral myelin, hypotonic swelling in the shiverer membrane arrays occurs in the extracellular space between membranes; the cytoplasmic surfaces remain closely apposed notwithstanding the absence of basic protein from this region. Surprisingly, we found that the interaction at the extracellular apposition of shiverer membranes is altered. The extracellular space swells to a greater extent than normal when nerves are incubated in distilled water, treated at a reduced ionic strength of 0.06 in the range of pH 4–9, or treated at constant pH (4 or 7) in the range of ionic strengths 0.02–0.20. To examine the biochemical basis of this difference in swelling, we compared the lipid composition of shiverer and normal myelin. We find that sulfatides, hydroxycerebroside, and phosphatidylcholine are 20–30% higher than normal; non-hydroxycerebroside and sphingomyelin are 15–20% lower than normal; and ethanolamine phosphatides, phosphatidylserine, and cholesterol show little or no change. A higher concentration of negatively charged sulfatides at the extracellular surface likely contributes to an increased electrostatic repulsion and greater swelling in shiverer. The cytoplasmic surfaces of the apposed membranes of normal and shiverer myelins did not swell apart appreciably in the pH and ionic strength ranges expected to produce electrostatic repulsion. This stability, then, clearly does not depend on basic protein. We propose that P0 glycoprotein molecules form the stable link between apposed cytoplasmic membrane surfaces in peripheral myelin.
    Materialart: Digitale Medien
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  • 39
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Retrograde axonal transport of phospholipid was studied in rat sciatic motoneuron axons by placing collection crushes on the nerve at intervals after injection of [methyl-3H]choline into the lumbosacral spinal cord, and allowing labelled material undergoing anterograde or retrograde movement to accumulate adjacent to the collection crushes. Control experiments showed that the accumulations of label were not a result of local uptake of circulating precursor. The majority of the 3H label was associated with phosphatidylcholine. Accumulation of label at the distal collection crush, representing retrograde transport, was observed subsequent to the anterograde transport of phospholipid. In comparison with previous study on retrograde transport of protein, the following points were noted: (1) onset of retrograde transport occurred at approximately the same time after precursor injection (10–20 h) for both protein and phospholipid; (2) retrograde transport of lipids was more prolonged: maximum retrograde transport occurred later for phospholipid (30 h) than for protein (15–20 h), and declined to half-maximum between 49 and 99 h, compared to a corresponding value of 24–28 h for protein; (3) the proportion of total anterograde-transported activity subsequently undergoing retrograde transport was less in the case of phospholipid, at least over the time interval studied (up to 99 h after precursor injection). The similar times of onset of retrograde transport of phospholipid and protein support the concept of retrograde transport as a recycling mechanism returning to the cell body membrane fragments that were earlier transported into the axon. Coordinated retrograde transport of labelled protein and phospholipid components of the recycled membranes would be predicted. Differences between protein and phospholipid in the subsequent time course and amount of retrograde transport may reflect differences in axonal handling of protein and lipid. Both the more prolonged outflow of labelled lipids from cell body into axon and exchange with a distal pool of unlabelled phospholipid may account for the prolonged time course of retrograde transport of labelled lipid.
    Materialart: Digitale Medien
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  • 40
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Materialart: Digitale Medien
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  • 41
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Materialart: Digitale Medien
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  • 42
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The existence of a mechanism by which the ester- and ether-linked aliphatic chains of the major phospholipids are retailored during their axonal transport and sorted to specific membrane systems along the optic nerve and tract was investigated. A mixture of [I-14C]hexadecanol and [3H]arachidonic acid was injected into the vitreous body of albino rabbits. At 24 h and 8 days later, the distribution (as measured by the 3H/14C ratio) and the positioning (as monitored by hydrolytic procedures) of radioactivity in the various phospholipid classes of retina, purified axons, and myelin of the optic nerve and tract were determined. At the two intervals after labeling, the 3H/14C ratios of each diradyl type of phosphatidylethanolamine and phosphatidylcholine were (a) substantially unchanged all along the axons within the optic nerve and tract and (b) markedly modified in comparison with those found in the retina and axons for molecular species selectively restricted to myelin sheath. Evidence is thus available that intraxonally moving ethanolamine and choline glycerophospholipids, among others, are added to axonal membranes most likely without extensive modifications. In contrast, they are transferred into myelin after retailoring. Through these two processes, the sorting and targeting of newly synthesized phospholipids to their correct membrane domains. such as axoplasmic organelles, axolemma, or periaxonal myelin, could be controlled.
    Materialart: Digitale Medien
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  • 43
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Adrenal medullary chromaffin cells were maintained under conditions known to increase their cellular levels of enkephalin-containing peptides and the effects of these treatments on another chromaffin vesicle component, dopamine β-hydroxylase, were examined. Catecholamine-depleting drugs, such as tetrabenazine, and cyclic nucleotide-elevating drugs, including forskolin, 8bromo-cyclic AMP, and theophylline, increase chromaffin cell enkephalin-containing peptide levels but fail to increase dopamine β-hydroxylase. In contrast, insulin treatment increases the levels of both enkephalin-containing peptides and dopamine β-hydroxylase. The increased amounts of enkephalin-containing peptides produced by tetrabenazine and by insulin are stored in subcellular particles with properties identical to chromaffin vesicles on density-gradient centrifugation. These results suggest that following insulin treatment chromaffin cells synthesize new chromaffin vesicles with a full complement of enkephalin-containing peptides, but that after treatment with catecholamine-depleting or cyclic nucleotide-related agents enkephalin-containing peptides can be inserted into preexisting vesicles or that new vesicles, made as a part of the normal turnover of cellular components, contain elevated peptide levels.
    Materialart: Digitale Medien
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  • 44
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Experiments were performed to demonstrate the involvement of electron transport system in fatty acid elongation in rat brain microsomes. Mercuric chloride and p-chloromercuriphenylsulfonate, inhibitors on NADH-cytochrome b5 reductase, at 32 μM inhibited NADH-supported palmitoyl-CoA elongation to 30 and 60% of control activity, respectively, whereas NADPH-supported palmitoyl-CoA elongation was unaffected by these mercurials. An antibody to rat liver NADH-cytochrome b5 reductase inhibited brain microsomal NADH-cytochrome b5 reductase activity and NADH-dependent palmitoyl-CoA elongation. Treatment of brain microsomes with trypsin diminished the cytochrome b5 content; NADH- and NADPH-cytochrome c reductase activities were significantly decreased, but the decrease in NADH-cytochrome b5 reductase activity was relatively small. Whereas essentially no incorporation of malonyl-CoA into palmitoyl-CoA was observed with trypsintreated microsomes, addition of detergent-solubilized cytochrome b5 resulted in a recovery of fatty acid elongation. These results indicate the presence of an electron transport system, NADH-NADH-cytochrome b5 reductase–cytochrome b5-fatty acid elongation, in brain microsomes.
    Materialart: Digitale Medien
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  • 45
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Capillaries in vertebrate brain have unique permeability properties that make up the blood–brain barrier (BBB). Although it is known that capillaries are innervated by nerve endings of intracerebral origin and that brain capillary function is likely acutely regulated by neuronal inputs, the possible mechanisms of neuronal regulation of capillary function are at present unknown. One possible mode of regulation is via the phosphorylation of brain capillary proteins. The present studies characterize, for the first time, the major phosphoproteins in the bovine brain capillary using both intact bovine brain capillaries and plasma membrane fractions from bovine brain capillaries. The patterns of endogenous phosphorylation of capillary proteins are compared to similar patterns obtained with synaptosomal (P2) fractions from bovine brain. The major findings of this study are: (a) The activity of protein phosphorylation in brain capillaries is localized almost exclusively to the capillary plasma membrane, and is nearly comparable to the activity of protein phosphorylation in synaptosomal membranes. (b) A major phosphoprotein doublet in the capillary fraction comigrates on a sodium dodecyl sulfate gel with a major phosphoprotein doublet of approximate molecular weight of 80K in the synaptosomal fraction, and the latter is presumed to be synapsin I; in dephosphorylation assays the synaptosomal 80K phosphoprotein doublet is not subject to measurable dephosphorylation, whereas the capillary 80K doublet is subject to rapid dephosphorylation, and is essentially completely dephosphorylated within 5 s at 0°C. (c) A prominent triplet of phosphoproteins with molecular weight of 50–55K is present in the capillary fraction, and is not present in the synaptosomal fraction; thus, this 50—55K triplet of phosphoproteins appears specific for brain capillaries. In summary, these studies provide the basis for future investigations of a protein phosphorylation paradigm in regard to the rapid control of brain capillary function by brain.
    Materialart: Digitale Medien
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  • 46
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Adenylate cyclase activity in bovine cerebellar membranes is regulated by calmodulin, forskolin, and both stimulatory (Ns) and inhibitory (Ni) guanine nucleotide-binding components. The susceptibility of the enzyme to chymotrypsin proteolysis was used as a probe of structure-function relationships for these different regulatory pathways. Pretreatment of membranes with low concentrations of chymotrypsin (1–2 μg/ml) caused a three- to fourfold increase in basal adenylate cyclase activity and abolished the Ca2+-dependent activation of the enzyme by calmodulin. In contrast, the stimulation of the enzyme by GTP plus isoproterenol was strongly potentiated after protease treatment, an effect that mimics the synergistic activation of adenylate cyclase by Ns and calmodulin in unproteolyzed membranes. Limited proteolysis revealed low- and high-affinity components in the activation of adenylate cyclase by forskolin. The lowaffinity component was readily lost on proteolysis, together with calmodulin stimulation of the enzyme. The activation via the high-affinity component was resistant to proteolysis and nonadditive with the Ns-mediated activation of the enzyme, suggesting that both effectors utilize a common pathway. The inhibitory effect of low concentrations (10−7M) of guanyl-5′-yl imidodiphosphate [Gpp(NH)p] on forskolin-activated adenylate cyclase was retained after limited proteolysis of the membranes, indicating that the proteolytic activation does not result from an impairment of the Ni subunit. Moreover, in the rat cerebellum, proteolysis as well as calmodulin was found to enhance strongly the inhibitory effect of Gpp(NH)p on basal adenylate cyclase activity. Our results suggest that calmodulin and Ns/Ni interact with two structurally distinct but allosterically linked domains of the enzyme. Both domains appear to be involved in the mode of action of forskolin.
    Materialart: Digitale Medien
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  • 47
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Glutamate analogues have been used in many different experimental approaches in neurobiology. A small number of these analogues have been classified as gliotoxic. We have examined the effect of seven glutamate analogues (five gliotoxic and two neurotoxic) on the growth and viability of four human glioma cell lines, one human medulloblastoma cell line, and one human sarcoma cell line. Aminoadipic acid and homocysteic acid predominantly affected the growth of two glioma cell lines in the presence of 4 mM glutamine. Phosphonobutyric acid predominantly affected the other two glioma cell lines and the medulloblastoma cell line in the presence of 4 mM glutamine. In medium containing no glutamine, all three analogues had marked effects on all the cell lines except the sarcoma cell line. These effects were dose dependent. We postulate that these results can in part be explained on the basis of metabolic compartmentalization.
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  • 48
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: This report presents the neurochemical findings on the first dog to die with deficiency of α-L-iduronidase (mucopolysaccharide α-L-iduronohydrolase; EC 3.2.1.76). The principal findings were (a) markedly increased glycosaminoglycan content in all neural tissues examined (from threefold in sciatic nerve to 15-fold in brainstem), (b) a modest increase in levels of gangliosides GM2, GM3, and GD3, particularly in gray matter, (c) excessive accumulation of glycosaminoglycans in the CSF, (d) the increased glycosaminoglycans were dermatan sulfate and heparan sulfate, and (e) the molecular weights of the liver glycosaminoglycans were shifted toward smaller sizes, indicating partial degradation. The canine disorder thus resembles mucopolysaccharidosis I in all aspects.
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  • 49
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The incorporation of tritium from NaB3H4 into the major protein components of myelin and the presence of weak fluorescence emission bands at wavelengths of –440 and 500.nm from sodium dodecyl sulfate-solubilized, delipidated white matter are indicative of the presence of the products of aldehyde reactions with proteins. The incorporation of tritium from NaB3H4 into myelin proteins was confirmed by reaction with purified components of myelin basic protein or with lipophilin, a purified fraction of proteolipid protein. From the extent of tritium incorporation into the purified proteins, it is estimated that -0.2 mol of tritium is incorporated/mol of myelin basic protein and -0.4 mol of tritium/mol of proteolipid protein. There is -50% greater incorporation of tritium into a more degraded, less positively charged form of the basic protein. The incorporation of tritium into normal and multiple sclerosis white matter was compared. There is a small but statistically significant difference in the percentage of the total counts incorporated into the major protein fractions for the two groups, with the multiple sclerosis samples showing a higher percentage of the counts in the Wolfgram protein and a lower percentage in the myelin basic protein compared with the normal samples.
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  • 50
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Microtubules purified from brain tissue contain endogenous cyclic AMP (cAMP)-dependent protein kinase activity, and microtubule-associated protein 2 (MAP2) is the major substrate. Beef brain microtubules were prepared and used as a model system to study the differential effects of rationally selected cyclic nucleotide analogues on microtubule receptor protein kinase. Data are presented to indicate that the following molecular interactions are essential for activation of the phosphorylation of MAP2: (a) hydrogen bond formation toward the 2′, 3′, or 5’ position, (b) interaction with phosphorus, and (c) no hydrogen bonds but hydrophobic interactions at the base moiety. Thus, the activation mechanism of the type II protein kinase associated with brain microtubules resembles the mechanism found in protein kinases of other systems. In addition, we have studied the effect of the two diastereomers of adenosine 3′,5′-monophosphorothioate (cAMPS). The (Sp)-cAMPS isomer was found to activate MAP2 protein kinase, whereas the (Rp)-cAMPS isomer had no activating effect. In contrast, this compound was able to inhibit cAMP-stimulated MAP2 phosphorylation and thus acts as an antagonist of the Sp diastereomer and cAMP. Hence, this analogue provides a useful means to clarify further the effect of cAMP-dependent phosphorylation on functional properties in microtubules in general.
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  • 51
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Cholecystokinin octapeptide (CCK26–33) is metabolized by neural membranes with an initial cleavage to CCK29–33 and subsequent breakdown to CCK31–33 and CCK32–33; this pattern of proteolysis occurs on incubation with either P2 or purified lysed synaptosomal membranes. To determine whether the pattern of CCK26–33 proteolysis is unique to the brain and whether regional brain differences in its pathway or rate exist, we analyzed the proteolysis of CCK by synaptic membranes of various brain areas and cellular membranes of peripheral tissue. The pattern of degradation in brain did not differ among the regions studied. The overall proteolysis rate, as measured by the formation of tryptophan, was higher in the striatum than in the cortex, although CCK29–33 was formed at the same rate in both areas. In nonneural tissue, the rate of degradation was highest in liver membranes and lowest in pancreatic acinar cell preparations. Thus, it appears that degradative peptidases are not necessarily colocalized with CCK receptors. The pattern of product formation is the same in peripheral compared with CNS membranes; thus, the degradative pathway does not appear to be unique to brain tissue. The enzyme present in synaptic membranes that is responsible for CCK29–33 formation requires a metal ion and sulfydryl groups for the catalysis and thus is a metalloendopeptidase. Furthermore, its activity is inhibited by Ac-Gly-Phe-Nle-al, a peptide aldehyde whose sequence bears some homology to the amino acid sequence in the region of CCK26–33 that is cleaved by this enzyme.
    Materialart: Digitale Medien
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  • 52
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: t[3H]Butylbicycloorthobenzoate ([3H]TBOB; 22 Ci/mmol) was prepared by reductive dechlorination of its 4-chlorophenyl analog with tritium gas. This new radioligand binds reversibly to fresh washed rat brain P2 membranes in 500 mM NaCl plus 50 mM sodium-potassium phosphate buffer (pH 7.4) at 25°C, with 80–90% specific relative to total binding, a KD of 61 ± 15 nM, and a Bmax of 1.6 ± 0.5 pmol/mg of protein. [3H]TBOB association with its binding site(s) is monophasic, but its dissociation is biphasic. The binding characteristics of [3H]TBOB are essentially identical to those of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) with respect to pH dependence, stimulation by anions, regional distribution in the brain, and pharmacological profile. Saturation analyses and dissociation studies further indicate that TBOB and TBPS have a common binding site. However, binding of the two radioligands differs in respect to temperature effects. In contrast to [35S]TBPS, which exhibits negligible binding at 0°C, [3H]TBOB binds to rat brain membranes at 0, 25, and 37°C with similar KD values. [3H]TBOB with its long radioactive half-life and temperature-independent KD is a valuable supplement to [35S]TBPS in further biochemical and pharmacological characterization of the γ-aminobutyric acid receptor-ionophore complex.
    Materialart: Digitale Medien
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  • 53
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: CSF glutamine concentrations were studied in 12 patients with benign brain tumors (meningioma, craniopharyngioma, or osteofibroma), 12 patients with malignant brain tumors (astrocytoma, medulloblastoma, pinealoblastoma, or chondrosarcoma), 9 patients with non-cerebral tumors, and a reference group of 24 patients. The mean ± SD levels in the benign tumor group (424 ± 124 μM) were significantly lower (p 〈 0.0004) than those in the reference group (642 ± 195 μM). There was no significant difference between the CSF glutamine concentrations in the malignant cerebral tumor group (643 ± 210 μM) or noncerebral tumor group (599 ± 127 μM) and those in the reference group. In patients with benign brain tumors there was indication of an inverse linear relationship between the logarithm of CSF glutamine concentration and tumor diameter.
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  • 54
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: We previously observed that the neurotransmitter 5-hydroxytryptamine (5-HT, serotonin) binds with high- and low-affinity interactions to an actin-like protein prepared from rat brain synaptosomes. In this study, we examined its binding to highly purified actin obtained from rabbit skeletal muscle. Monomeric G-actin bound serotonin with high and low affinities, exhibiting equilibrium dissociation constants (KD values) of 5 × 10−5M and 4 × 10−3M, respectively. The serotonin binding site on actin was distinct from those sites previously characterized for divalent cations, nucleotides, and cytochalasin alkaloids. The binding of serotonin (1 μM) to G-actin was increased as much as 26-fold by divalent cations. Potassium iodine (KI) increased the affinity of G-actin for serotonin, KD values for this binding being 3 × 10−7M and 6 × 10−5M. Serotonin bound with even higher affinity to polymerized F-actin, with KD values of 2 × 10−8M and 2 × 10−5M. However, the total number of binding sites on F-actin was only about 4% of the number of G-actin. The binding of serotonin (0.1 μM) to G-actin could be inhibited by phenothiazines (1 μM) or reserpine (10 μM), but not by classical antagonists of serotonin receptors or by drugs that release serotonin or inhibit its uptake. The binding of serotonin to actin in vivo may participate in a contractile process related to neurotransmitter release.
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  • 55
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: A rat pheochromocytoma (PC12) cell line was used to examine the possibility that 5-hydroxytryptamine (serotonin), 3,4-dihydroxyphenylethylamine (dopamine), or noradrenaline may be associated with cytoplasmic actin, as was suggested by previous in vitro binding studies on an actin-like protein from rat brain synaptosomes. When PC12 cells were incubated with [3H]serotonin, [3H]dopamine, or [3H]noradrenaline for 30 min at 37°C, approximately 2–4% of the radioactivity present in the cells was found to be associated with a high-molecular-weight (actin-like) component in supernatant fractions. Evidence relating this monoamine binding component to actin filaments includes: (a) its strong absorption by myosin filaments at low ionic strength; (b) a decrease in its affinity for myosin in the presence of 1 mM ATP, which lowers the affinity of authentic actin for myosin; (c) displacement of bound [3H]serotonin from it by DNase I, which binds strongly to actin and which inhibits [3H]serotonin binding to actin in vitro; (d) an increase in its binding of each monoamine (by 25–40%) after PC12 cells were preincubated with 10 μM cytochalasin B (a drug that induces depolymerization of F-actin). These findings suggest that serotonin, dopamine, or noradrenaline may associate with actin filaments in vivo.
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  • 56
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Thirty minutes after the onset of darkness, ovine pineal arylalkylamine N-acetyltransferase, N-acetylserotonin, and melatonin increase 5- to 10-fold. No significant changes in hydroxyindole-O-methyltransferase, 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, 5-hydroxytryptophol, 5-methoxyindoleacetic acid, and 5-methoxytryptophol are detected at this time. Administration of cycloheximide inhibits the rise in N-acetyltransferase and N-acetylserotonin, but not melatonin. Unexpectedly, 5-methoxytryptophol increases after cycloheximide treatment. Taken together, these results, although consistent in part with a role for serotonin N-acetylation in the regulation of melatonin synthesis in sheep, indicate that an N-acetyltransferase-independent mechanism may also be involved.
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  • 57
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: An arylamine sulfotransferase (PST-M) from human brain cortex that is involved in the formation of O-sulfate esters of monoamines has been purified 272-fold by ammonium sulfate fractionation, gel filtration, DEAE-cellulose ion-exchange chromatography, chromatofocussing, and hydroxyapatite chromatography. A molecular weight of 62,000, pK of pH 5.8, and an optimum pH for the reaction at 7.8–8.0 with respect to tyramines have been determined. This enzyme possesses an extremely high affinity for dopamine and m-tyramine based on the low Km values and is moderately active toward noradrenaline and p-tyramine. Serotonin is a poor substrate. In contrast, another sulfotransferase, PST-P, which has been separated from PST-M and partially purified, exhibited a very high affinity for phenol and nitrophenols but was inactive toward the amine sulfate acceptors. In the human brain the specific activity toward dopamine as well as the ratio of activity toward dopamine/phenol was considerably higher than those for rat, hog, and bovine brains.
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  • 58
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Nerve growth factor (NGF)-untreated (naive) and neurite-bearing NGF-treated (“primed”) PC12 rat pheochromocytoma cells were used as model system to study the role of phospholipid methylation in the NGF mechanism of action. The neurite-bearing cultures were deprived of NGF for 3 h before experimentation. Under both experimental conditions, the cells were labelled with [methyl-3H]methionine and then challenged with NGF for time periods ranging from 5 s to 30 min. Methylated phospholipids were extracted and then resolved and identified by TLC as phosphatidyl mono-, di-, and trimethyl ethanolamine. Quantification of the amount of radioactivity incorporated into each of the phospholipids indicated that NGF does not significantly alter phospholipid methylation either in naive or in neurite-bearing cells. Furthermore, using a methyltransferase inhibitor, it was found that neurite outgrowth still occurs when phospholipid methylation is almost completely blocked. These results indicate that phospholipid methylation does not play a primary role in the mechanism of action of NGF.
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  • 59
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: A complex forms when bovine P2 protein is added to single-bilayer vesicles created by sonicating myelin lipids. The complex was studied by biochemical analysis, freeze-fracture (FF) and thin-section electron microscopy (EM), and by X-ray diffraction. Smaller amounts of P2 cause the vesicles to aggregate and fuse whereas larger amounts (〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:00223042:JNC844:ges" location="ges.gif"/〉4 wt%) cause multilayers to form. Binding saturates at 15 wt% P2. FF EM shows that large, flat multilayers form within 15 min of addition of P2. Only smooth fracture faces are seen, as expected for a peripheral membrane protein. X-ray diffraction shows a constant repeating distance in the multilayers: 86.0 ± 0.7 Å between the centers of bilayers in the range 4 wt%〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:00223042:JNC844:les" location="les.gif"/〉 P2/(P2 + lipid) 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:00223042:JNC844:les" location="les.gif"/〉15 wt%. Assuming a 53 Å-thick bilayer, the space between bilayers is 33 Å wide. This is a wider space than for myelin basic protein (MBP) (20–25 Å wide). The respective widths are consistent with a compact, globular structure for P2 and a flattened shape for MBP. Calculated electron-density profiles of the lipids with and without P2 reveal the protein largely in the interbilayer spaces, with a small part possibly inserted into the lipid headgroup layers. The different proportions of P2 in the sciatic nerve of various species are tentatively correlated with the different average widths observed by X-ray diffraction for the cytoplasmic space (major period line) between bilayers in the respective sciatic myelins.
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  • 60
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Polypeptides in the motor axons of the sciatic nerve in 120-day-old normal and diabetic mice C57BL/Ks (db/db) were labeled by injection of [35S]methionine into the ventral horn of the spinal cord. At 8, 15, and 25 days after the injection, the distribution of radiolabeled polypeptides along the sciatic nerve was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Four major radiolabeled polypeptides, tentatively identified as actin, tubulin, and the two lightest subunits of the neurofilament triplet, were studied in both diabetic and control mice. In the diabetic animals, the two polypeptides identified as actin and tubulin showed a reduction of average velocity of migration along the sciatic nerve, resulting in a higher fraction of radioactivity in the proximal part of the sciatic nerve, whereas the front of radioactivity (advancing at maximal velocity) moved at a normal rate. In contrast, both the average and maximal velocities of the two neurofilament subunits were slower in the diabetic mice than in the control mice. These results indicate that the axonal transport of the cytoskeletal proteins is differentially affected in the course of diabetic neuropathy, and may suggest that the impairment concerns mainly the proteins carried by the slowest component of axonal transport.
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  • 61
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: N-Acetyltransferase (NAT) is an enzyme whose rhythmic activity in the pineal gland and retina is thought to be responsible for melatonin circadian rhythms. The enzyme has circadian properties–its rhythm persists in constant conditions, and it is precisely controlled by light and dark. Experiments are reported in which 4-h light or dark pulses were imposed on chicks (Gallus domesticus) over a 24-h period. Pineal NAT profiles were measured during and subsequent to the pulses. The phase of the NAT cycle following pulses was plotted to obtain phase-response curves. Light pulses produced a maximum phase shift (advance of 5 h) 8 h after the expected time of lights-out; dark pulses produced a maximum phase shift (advance of 4 h) 3 h after the expected time of lights-out. Maximum phase delays (−2 h) occurred 1–2 h after the expected lights-out for light pulses and 8 h after expected lights-on for dark pulses.
    Materialart: Digitale Medien
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  • 62
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Previous studies have provided evidence for adrenocorticotropic hormone (ACTH) effects on a wide variety of behaviors. However, the precise sites of action and the mechanisms by which these effects may be mediated have yet to be clearly elucidated. Although ACTH was shown to augment cyclic AMP levels in glial cells isolated from whole brain, other studies found little or no effect of ACTH peptides on cyclic nucleotide metabolism in slices of cerebral cortex or homogenates of whole brain. In the present study, our objective was to determine whether ACTH peptides regulate intracellular cyclic AMP levels in neurons of the cerebral cortex in primary culture. ACTH peptides stimulated cyclic AMP synthesis up to threefold in a dose-dependent manner; stimulation was complete within 5–10 min of exposure to agonists. Neurohormone efficacy was augmented by 0.1 μM forskolin (which was virtually ineffective alone); potency was unaffected. The order of potency (EC50) for increasing intracellular cyclic AMP levels was as follows: ACTH (1–24), ACTH (1–17) (10 nM) 〉 α-melanocyte stimulating hormone, β-melanocyte stimulating hormone (α-MSH, β-MSH) (100 nM) 〉 ACTH (1–10) (1 μM) 〉 ACTH (4–10) (5 μM). The hexapeptide ACTH (4–9) as well as ACTH (11–24) were inactive at concentrations as high as 10 μM. Other neuropeptides derived from proopiocortin, such as β-endorphin and Met- and Leu-enkephalin were without effect on basal or hormonally stimulated cyclic AMP synthesis. In order to determine whether distinct receptors for ACTH are present on cortical neurons, saturating concentrations of the peptide were coincubated with either vasoactive intestinal polypeptide (VIP) or the β-adrenergic agonist, isoproterenol (INE). The response to combinations of ACTH and INE were clearly additive. However, neither ACTH nor INE could further augment cyclic AMP formation at saturating concentrations of VIP. Comparison of structure-activity relationships suggest that ACTH receptors mediating the elevation of cyclic AMP formation in cortical neurons may be similar to those associated with the peptide actions on arousal rather than conditioned behavior.
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  • 63
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The relationship between phenolsulfotransferase (PST) and catechol-O-methyltransferase (COMT) in the metabolism of free 3,4-dihydroxyphenylethylamine (DA, dopamine) in the rat brain was studied. In rats not pretreated with a monoamine oxidase (MAO) inhibitor a huge increase of free DA in the brain, following an intraperitoneal injection of L-3,4-dihydroxyphenylalanine (L-DOPA) or an intraventricular injection of free DA, did not lead to any noticeable change in DA sulfate or 3-methoxytyramine (3-MT), which remained undetectable by the present HPLC method. However, in rats previously treated with the MAO inhibitors pargyline or tranylcypromine, the same L-DOPA or free DA treatment resulted in significant increases in both 3-MT and DA sulfate in the hypothalamus, brainstem, and striatum. This response of COMT and PST was not affected by prior treatment of the rats with 6-hydroxydopamine, which suggests that O-methylation and sulfoconjugation occur outside adrenergic neurons not destroyed by the neurotoxin. Inhibition of COMT activity did not lead to any increase in DA sulfate, which showed that despite their common mode of action (both enzymes react preferentially at the same hydroxyl group in the DA molecule), the two enzymes are not competitive. After MAO inhibition there were strong correlations between an increase in DA sulfate and 3-MT on the one hand, and between free DA and 3-MT on the other. Because 3-MT is a marker of central DA release, these data suggest that inhibition of MAO activity not only affects DA metabolism by this enzyme but also influences DA release in the rat brain.
    Materialart: Digitale Medien
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  • 64
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Book reviewed in this article: Functional Properties of Cortical Cells (Cerebral Cortex Vol. 2) edited by E. G. Jones and A. Peters. Neural Transplants. Development and Function edited by J. R. Sladek, Jr. and D. H. Gash. Current Topics in Research on Synapses, Volumes 1 and 2 edited by D. G. Jones, Alan R. Liss
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  • 65
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The behavior of oligodendrocyte chromatin after micrococcal nuclease digestion of nuclei was assayed in brains of rats of four different ages. During oligodendrocyte differentiation, a decreasing sensitivity of the chromatin to enzymatic attack was observed. On the other hand, the nucleosomal repeat length showed a slight tendency to increase during development. It is worth noting that even the highest values reported here for “oligodendrocyte’ chromatin repeat lengths are significantly lower than 200 base pairs, the value previously reported by others for “non-astrocytic glia.”
    Materialart: Digitale Medien
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  • 66
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Choline acetyltranferase activity was investigated in the superior cervical ganglia and in six microdissected regions of the medulla oblongata of the rat ipsilateral and contralateral to electrolytic lesions of the trigeminal sensory ganglia (Gasserian). Electrolytic lesions of the Gasserian ganglia failed to modify levels of enzymatic activity in all structures studied. This result would be an argument against the existence of a major cholinergic population of sensory neurones in the trigeminal system.
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  • 67
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: We examined autopsied brain from 10 patients with end-stage renal failure who had undergone repeated hemodialysis. Eight had classic symptoms, and two had suggestive symptoms of dialysis encephalopathy. Findings were compared with those in autopsied brain from control adults who had never been hemodialyzed. Mean γ-aminobutyric acid (GABA) contents were significantly reduced in frontal and occipital cortex, cerebellar cortex, dentate nucleus, caudate nucleus, and medial-dorsal thalamus of the hemodialyzed patients, the reduction being 〉40% in cerebral cortex and thalamus. Choline acetyltransferase activity was reduced by 25–35% in three cortical regions in the hemodialyzed patients. These two abnormalities were observed in the brain of each hemodialyzed patient, regardless of whether or not the patient died with unequivocal dialysis encephalopathy. Pyridoxal phosphate contents were substantially reduced in brains of the hemodialyzed patients, but metabolites of noradrenaline, 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (serotonin) were present in normal amounts. Aluminum levels were abnormally high in frontal cortical gray matter in the hemodialyzed patients. Although this study does not clarify the role played by aluminum toxicity in the pathogenesis of dialysis encephalopathy, the abnormalities we found suggest the need for further neurochemical investigations in this disorder.
    Materialart: Digitale Medien
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  • 68
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Saturable and stereoselective binding sites for [3H]threo-(±)-methylphenidate were characterized in rat brain membranes. The highest density of [3H]threo-(±)- methylphenidate binding sites was found in the synapto somal fraction of corpus striatum. Scatchard analysis revealed a single class of noninteracting binding sites with an apparent dissociation constant (KD) of 235 nM and a maximum number of binding sites (Bmax) of 13.4 pmol/mg protein. Saturable, high-affinity binding of [3H]threo-(±)-methylphenidate to striatal synaptosomal membranes was dependent on the presence of sodium ions. A good correlation (r = 0.88; p 〈 0.001) was observed between the potencies of various psychotropic drugs in displacing [3H]threo-(±)-methylphenidate from these sites and their potencies as inhibitors of [3H]3,4-dihydroxyphenylethyl- amine ([3H]dopamine) uptake into striatal synaptosomes. A good correlation (r = 0.85; p 〈 0.001) was also observed between the potencies of a series of ritalinic acid esters in inhibiting [3H]threo-(±)-methylphenidate binding to striatal synaptosomal membranes and their potencies as motor stimulants in mice. These observations suggest that the binding sites for [3H]threo-(±)-methyl-phenidate described here are associated with a dopamine uptake or transport complex, and that these sites may mediate the motor stimulant properties of ritalinic acid esters such as methylphenidate.
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  • 69
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The differential effects of muscarinic agents on inositol phospholipid hydroilysis and the role in this process of putative muscarinic receptor subtypes (M1 and M2) were investigated in three regions of guinea pig brain. Addition of the agonist oxotremorine-M to slices of neostriatum, cerebral cortex, or hippocampus incubated in the presence of myo-[2-3H]inositol and Li+ resulted in a large accumulation of labeled inositol phosphates (733, 376, and 330% of control, respectively). In each tissue, the principal product formed was myo-inositol 1-phosphate (59–86%), with smaller amounts of glycerophosphoinositol and inositol bisphosphate. Only trace amounts of inositol trisphosphate could be detected. Regional differences were observed in the capacity of certain partial agonists to evoke inositol lipid hydrolysis, the most notable being that of bethanechol, which was four times more effective in the neostriatum than in either the cerebral cortex or hippocampus. In addition, the full agonists, oxotremorine-M and carbamoylcholine, were more potent stimulators of inositol phosphate release in the neostriatum than in the cerebral cortex. The putative M1 selective agonist 4-m-chlorophenylcarbamoyloxy-2-butynyl trimethyl ammonium chloride had little stimulatory effect in any brain region, whereas the putative M1 selective antagonist pirenzepine blocked the enhanced release of inositol phosphates with high affinity in the cerebral cortex and hippocampus (Ki = 12.1 and 13.9 nM; “M1”) but with a lower affinity in the neostriatum (Ki = 160 nM; “M2”). In contrast to its differential effects on stimulated inositol lipid hydrolysis, no regional differences were observed in the capacity of pirenzepine to displace [3H]quinuclidinyl benzilate, a muscarinic antagonist, bound to membrane fractions. Atropine, an antagonist that does not discriminate between receptor subtypes, inhibited the enhanced release of inositol phosphates with similar affinities in the three regions (Ki = 0.40–0.60 nM). The results indicate that by measurement of inositol lipid hydrolysis, regional differences in muscarinic receptor coupling characteristics become evident. These differences, which are not readily detected by radioligand binding techniques, might be accounted for by either the presence of functionally distinct receptor subtypes, or alternatively, by regional variations in the efficiency of muscarinic receptor coupling to inositol lipid hydrolysis.
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  • 70
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Fresh myelin, isolated from brainstems of adult rats, was incubated in the presence of Cu2+ and H2O2. Electrophoretic analysis of the reisolated myelin membrane revealed a gradual loss of the protein moiety from the characteristic pattern and an increase in aggregated material appearing at the origin of the gel. The aggregation of proteins was time-dependent and was concomitant with the accumulation of lipid peroxidation products reactive with thiobarbituric acid. Furthermore, during the course of incubation, there was a gradual decrease in the amount of recovered light myelin and a quantitatively similar increase in heavier myelin subfractions. The aggregation of proteins seems not to be directly related to the buoyant densities of myelin fragments. The peroxidative damage to the myelin proteins may be an important contributor to pathochemistry of myelin sheath, in particular, and in general it implies the susceptibility of the protein moiety of cell membranes to oxygen-induced deterioration.
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  • 71
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Postsynaptic densities (PSDs) were prepared by the aqueous two-phase extraction of synaptic membranes in the presence of n-octyl glucoside. Incubation of postsynaptic densities with [γ-32P]ATP resulted in the incorporation of 32P into a range of proteins. Isolation of glycoproteins from 32P-labelled PSDs by affinity chromatography on concanavalin A-agarose identified the postsynaptic glycoprotein of apparent M, 180,000 (gp180) as a substrate for endogenous protein kinase(s). When the phosphorylation reaction was performed in the presence of Ca2+ and calmodulin, there was an overall 13- fold increase in the phosphorylation of PSD proteins. The largest effects of calmodulin were associated with two proteins of molecular weights 51,000 and 60,000, which showed average calmodulin-dependent increases in phosphorylation of 68-fold. The phosphorylation of gp180 was increased 7.5-fold in the presence of calmodulin. Fifty percent of maximum phosphorylation of proteins and glycoproteins occurred with a free Ca2+ concentration of 0.3 × 10−6M. The amounts 12.6 μg/ml and 9.1 μg/ml of calmodulin were required for 50% of maximum phosphorylation of proteins and glycoproteins, respectively. Peptide mapping experiments identified three major phosphorylation sites in gp180. The phosphorylation of all three sites was increased in the presence of calmodulin. Phosphoamino acid analysis of gp180 revealed that [32P]phosphoserine and [32P]phosphothreonine were both produced during the phosphorylation reaction, with phosphoserine being the predominant product. The phosphorylation of both amino acids was increased in the presence of calmodulin. [32P]phosphotyrosine was also identified as a product of the phosphorylation of gp180.
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  • 72
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The dependence on Na+, K+, and C1− of uptake and accumulation of [3H]noradrenaline was studied in plasma membrane vesicles isolated from PC-12 pheochromocytoma cells. Plasma membrane vesicles accumulated [3H]noradrenaline when an inward-directed gradient for Na+ and an outward-directed gradient for K+ were imposed across the vesicle membrane. Under these conditions, initial rates of uptake of [3H]noradrenaline were saturable (Km= 0.14 μM) and inhibited by a series of substrates and inhibitors of “uptake1.’ The IC50 values were positively correlated with those for inhibition of uptake into intact PC-12 cells. Uptake and accumulation [3H]noradrenaline in plasma membrane vesicles were absolutely dependent on external Na+ and C1−; they were dependent on an inwardly directed gradient for Na+ but less dependent on an inwardly directed gradient for C1−. Internal K+ strongly enhanced uptake and accumulation of [3H]noradrenaline. Rb+, but not Li+, had the capacity to replace internal K+. Two explanations are proposed for this effect of internal K+: (a) creation of a K+ diffusion potential (inside negative) provides a driving force for inward transport, and/or (b) K+ increases the turnover rate by formation of a highly mobile potassium–carrier complex. A hypothetical scheme for the transport of noradrenaline is presented.
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  • 73
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The effect of N-methyl-d,l-aspartic acid (NMA) on extracellular amino acids was studied in the rabbit hippocampus with the brain dialysis technique. Administration of 0.5 or 5 mM NMA caused a concentration-dependent liberation of taurine and phosphoethanolamine (PEA). Taurine increased by 1,200% and PEA by 2,400% during perfusion with 5 mM NMA whereas most other amino acids rose by 20–100%. The effect of NMA appeared to be receptor-mediated, as coperfusion with D-2-amino-5-phosphonovaleric acid curtailed the NMA response by some 90%. The NMA-stimulated release of taurine and PEA was suppressed when Ca2+ was omitted and further inhibited when Co2+ was included in the perfusion medium. The effect of NMA was mimicked by the endogenous NMA agonist quinolinic acid and the partial NMA agonist d,l-cis-2,3-piperidine dicarboxylic acid. Although the NMA-evoked release of taurine and PEA was Ca2+-dependent in vivo, NMA had no effect on Ca2+ accumulation in hippocampal synaptosomes. The previously reported NMA-induced activation of dendritic Ca2+ spikes and the lack of effect on synaptosomal Ca2+ uptake suggest that taurine and PEA are released from sites other than nerve terminals, possibly from dendrosomatic sites. This notion was strengthened by the absence of an effect of NMA on the efflux of radiolabelled taurine from hippocampal synaptosomes. In contrast, high K+ stimulated synaptosomal uptake of Ca2+ and release of taurine.
    Materialart: Digitale Medien
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  • 74
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Developing oligodendrocytes cultured in vitro express glycerol phosphate dehydrogenase (GPDH; EC 1.1.1.8) and are known to respond to glucocorticoid treatment by increased activity of GPDH. We present evidence that GPDH is enriched in white matter and oligodendrocytes of adult pig brain. Bulk-isolated oligodendrocytes maintained in culture for several weeks exhibit an almost constant level of GPDH activity. Furthermore, a 4-day stimulation with hydrocortisone induces GPDH specific activity of long-term cultured oligodendrocytes from adult pig brain.
    Materialart: Digitale Medien
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  • 75
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Guinea pig brain cortex synaptosomes and neurosecretory PC12 cells were loaded with [3H]3,4-di-hydroxyphenylethylamine ([3H]DA, [3H]dopamine) and then exposed to leptinotoxin-h (LPTx) (purified and partially purified preparations, obtained from the hemo-lymph of Leptinotarsa haldemani). In a Ca2+-containing Ringer medium the toxin induced prompt and massive release of the neurotransmitter. Half-maximal effects were obtained at concentrations estimated of approximately 3 × 10−11M for synaptosomes, and 1.5 × 10−10M for PC12 cells. Release responses in the two experimental systems investigated were dependent to different extents on the Ca2+ concentration in the medium. In synaptosomes clear, although slow, release of [3H]DA was elicited by the toxin even in Ca2+-free, EGTA-containing medium, provided that high (in the 10−10M range) concentrations were used; near-maximal responses were observed at 10−5M Ca2+. In contrast, the toxin-induced release from PC12 cells was appreciable only at 3 × 10−5M Ca2+, and was maximal at 2 × 10−4M and above. In both synaptosomes and PC12 cells Sr2+ and Ba2+ could substitute for Ca2+; Co2+ was inhibitory, whereas Mn2+ failed to modify the release induced by the toxin in Ca2+-containing medium. Organic blockers of the voltage-dependent Ca2+ channel (verapamil and nitrendipine) and calmodulin blocking drugs (trifluoperazine and calmidazolium) failed to inhibit the toxin-induced release of [3H]DA. LPTx induced profound morphological effects. Synaptosomes treated in the Ca2+-containing medium exhibited fusion of synaptic vesicles, formation of numerous infoldings and large cisternae, and alterations of mitochondria. In the Ca2+-free medium the effects were similar, except that their appearance was delayed, and mitochondria were well preserved. Swelling was observed in PC12 cells, accompanied by enlargement of the Golgi area, accumulation of multivesicular bodies, mitochondrial alterations, and decreased number of secretion granules (Ca2+-containing medium). Morphometric analyses revealed a good correlation between the decrease of both synaptic vesicles (synaptosomes) and neurosecretory granules (PC12 cells), and the release of [3H]DA measured biochemically. This is a good indication that the release effect of the toxin is due to stimulation of exocytosis. Taken as a whole, these results confirm the similarity of the effects of LPTx with α-latrotoxin of the black widow spider venom, mentioned in the companion article. However, differences in effect and target specificity suggest that the two toxins are specific to separate binding sites. Because of its profound and exclusively presynaptic effects LPTx promises to be an interesting tool for the study of the regulation of exocytotic neuro-transmitter release.
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  • 76
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Translation products of mRNA from retinas of goldfish optic nerve (representing a regenerative CNS) and adult rabbit optic nerve (representing a nonregenerative CNS which can be induced to express regenerative characteristics) were examined by one- and two-dimensional gel electrophoresis. Translation products from retinas of the regenerating goldfish optic nerve included polypeptides barely detectable in the translation products of mRNA derived from retinas of uninjured controls. Some of these polypeptides, of apparent molecular weights 24–28, 43–49, 60, and 65 kilodaltons can be considered as growth-associated polypeptides described in other regenerative and developing systems. The induction of regeneration-associated characteristics in the injured adult rabbit optic nerve, “implanted” with diffusible substances from nonneuronal cells of regenerative or growing nerve, is reflected by changes in the mRNA translation products of the retina. Among such translation products are those of the following molecular weights: 16–18, 28, 32–35, 43–47, and 56–60 kilodaltons, and some higher-molecular-weight species.
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  • 77
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Previous results demonstrate that hypoxia (low oxygen) diminishes calcium uptake by synaptosomes. The present studies examined the effects of low oxygen on calcium homeostasis in the digitonin-resistant (mitochondrial) and the digitonin-labile (nonmitochondrial) compartments of intact synaptosomes and their relation to altered membrane potentials. A 10-min hypoxic incubation in low-potassium media reduced total (-38.3%), mitochondrial (-43.3%), and nonmitochondrial (-27.8%) calcium uptake. In high-potassium media, low oxygen reduced mitochondrial (-41.2%) and total (-34.4%) uptake whereas nonmitochondrial (+6%) calcium uptake was essentially unaffected. A temporal analysis of nonmitochondrial calcium uptake revealed an initial depression (0–5 min) followed by a stimulation (5–10 min). Hypoxic-induced alterations in the subsynaptosomal distribution of calcium resembled those produced by uncouplers [FCCP (carbonylcyanide-p-trifluoro-methoxyphenylhydrazone) or rotenone plus oligomycin]. 3,4-Diaminopyridine partially ameliorated the hypoxic-and FCCP-induced decreases in synaptosomal calcium uptake. Low oxygen reduced the total synaptosomal membrane potential (i.e., plasma plus mitochondrial membrane potential) as measured by an increased efflux of tetraphenylphosphonium ion. This hypoxic-induced efflux of tetraphenylphosphonium was slowed by pretreatment with 3,4-diaminopyridine. Thus, both drug and membrane potential studies suggest that hypoxic-induced alterations in the subcellular distribution of calcium may be due to an uncoupling mechanism and a collapse of the synaptosomal mitochondrial membrane potential.
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  • 78
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Sprague-Dawley dams were fed either a protein-calorie deficient or control diet from day 5 to day 21 after parturition. The concentrations of seven amino acids (aspartate, glutamate, γ-aminobutyric acid, glycine, glutamine, serine, and taurine) were determined in brain regions from 17-day-old undernourished offspring and from 35-day-old rehabilitated rats. The brain regions examined were the cortex, cerebellum, corpus striatum, hippocampus, hypothalamus, brainstem, and midbrain. At 17 days of age, taurine was the amino acid with the highest concentration, whereas at 35 days glutamate had the highest concentration. This change was due to the fact that the concentration of taurine decreased significantly in all brain regions between 17 and 35 days, whereas the concentration of glutamate remained high or increased somewhat in all brain regions except the hypothalamus and brainstem. When the age-matched offspring of control and undernourished rats were compared, several interesting and significant differences were found. The concentrations of glutamate and aspartate were significantly lower (decreased 16–34%) in the cerebellum, brainstem, cortex, and midbrain in 17-day-old undernourished rats. The aspartate level was also significantly decreased in the corpus striatum and hypothalamus in 17-day-old offspring. However, the deficiencies of aspartate and glutamate were transient and reversible. In contrast, the concentration of taurine was increased in the hypothalamus (31%) and hippocampus (12–33%) at both 17 and 35 days of age and in the midbrain (17%) at 17 days. Other transient abnormalities in amino acid levels were found in undernourished offspring. The results of these experiments suggest that undernutrition during lactation causes delayed CNS development, which is manifested in altered concentrations of the neurotransmitters aspartate, glutamate, and taurine.
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  • 79
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The metabolism of acetate was investigated in the nerve-electroplaque system of Torpedo marmorata. In intact fragments of electric organ, radiolabeled acetate was incorporated into acetylcholine (ACh), acetylcarnitine (ACar), and three amino acids: aspartate, glutamate, and glutamine. These compounds were identified by TLC, high-voltage electrophoresis, column chromatography, and enzymic tests. The system responsible for acetate transport and incorporation into ACh displayed a higher affinity but a lower Vmax than that involved in the synthesis of ACar and amino acids. Choline, when added to the medium, increased the rate of acetate incorporation into ACh but decreased (at concentrations 〉10−5M) that into ACar and amino acids. Monofluoroacetate slightly depressed ACh and ACar synthesis from external acetate but inhibited much more the synthesis of amino acids. During repetitive nerve stimulation, the level of the newly synthetized [14C]ACh was found to oscillate together with that of endogenous ACh, but the level of neither [14C]ACar nor the 14C-labeled amino acids exhibited any significant change as a function of time. This means that there is probably no periodic transfer of acetyl groups between ACh and the investigated metabolites in the course of activity. Acetate metabolism was also tested in the electric lobe (which contains the cell bodies of the neurons innervating the electric organ) and in Torpedo synaptosomes (which are nerve terminals isolated from the same neurons). Radioactive pyruvate and glutamine were also assayed in some experiments for comparison with acetate. These observations are discussed in connection with ACh metabolism under resting and active conditions in tissues where acetate is the preferred precursor of the neurotransmitter.
    Materialart: Digitale Medien
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  • 80
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: [3H]γ-aminobutyric acid (GABA) was taken up by cultured embryonic retina cells during the initial stages of cell differentiation. The accumulated GABA was released in the bathing medium and a transient increase in the efflux of GABA was observed when cultures were pulse-stimulated (2 min) with 0.1 mM L-glutamate but not with D-glutamate. The EC50 for L-glutamate to evoke [3H]GABA release was approximately 15 μM. This value is close to the Km for high-affinity uptake of L-glutamate by retina cells. When Na+ ions were replaced by Li+ ions, L-glutamate-induced release of GABA was abolished. Moreover. L-[14C]glutamate uptake by retina cells was significantly reduced when NaCl was replaced by LiCl in the incubation medium. L-Glutamate elicited release of GABA was Ca2+ independent, and was observed when Ca2+ was replaced by Co2+ or when Mg2+ ions were increased to 10 mM concentration. D-Aspartate, which is taken up by the same high-affinity uptake mechanism as L-glutamate, induced an increase in [3H]GABA efflux comparable to L-glutamate. The addition of unlabeled GABA to the medium also promoted the release of accumulated [3H]GABA. However, GABA was twofold less effective than L-glutamate in eliciting [3H]GABA release. The addition of both GABA and L-glutamate to the incubation medium indicated that [3H]GABA efflux due to L-glutamate and GABA was additive. L-Aspartate also promoted an increase in the efflux of [3H]GABA accumulated by retina cells. However, L-aspartate effect was significantly decreased in the absence of Ca2+ or when Na+ ions were replaced by Li+. Our results indicate that at least three releasable pools of GABA are present in the chick embryo retina cells: (a) a GABA-promoted GABA release-homoexchange, (b) a Ca2+-dependent L-aspartate-promoted release, and (c) a Ca2+-independent, Na+-dependent L-glutamate-evoked release. In addition, our data strongly suggest that the L-glutamate-promoted GABA release is due to a process of exchange of L-glutamate with GABA, which may play a fundamental role in the fine control of the excitability of local circuits in the retina.
    Materialart: Digitale Medien
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  • 81
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The absolute amounts of precursor to ribosomal RNA (pre-rRNA) and ribosomal RNA (rRNA) in isolated rat brain neuronal and oligodendroglial nuclei were determined. The amount of the major pre-rRNA and rRNA species in neuronal nuclei was about twofold higher than in oligodendroglial nuclei. The relative rate of pre-rRNA synthesis in vivo was 2.3- to 2.7-fold higher in neuronal as compared with oligodendroglial nuclei. This corresponds to a 2.7-fold higher activity of the “template-bound” RNA polymerase I in isolated neuronal nuclei, whereas the activity of the “free” enzyme in both neuronal and glial nuclei was almost identical. The higher transcription rates of rRNA genes correlated with the markedly more prominent fibrillar component in neuronal nucleoli. The turnover times of the major pre-rRNA and rRNA species in neuronal and oligodendroglial nuclei were similar, except for 45S pre-rRNA, which turned over at an 1.5-fold slower rate in neuronal nuclei. The relative rates of processing of pre-rRNA and of nucleocytoplasmic transport of rRNA in neuronal cells were 2.7-fold higher than in oligodendroglial cells and corresponded to the differences in rRNA gene transcription rates. The established ribosome formation features correlated with an abundant (neurons) or exceedingly scarce (oligodendrocytes) nucleolar granular component. The turnover rate of cytoplasmic ribosomes in rat brain neurons was twofold slower than in oligodendrocytes, largely because of the about fivefold higher amount of ribosomes in the cytoplasm of neurons. We conclude that ribosome formation and turnover in neuronal and oligodendroglial cells are adapted to the protein synthetic levels in these two types of brain cells.
    Materialart: Digitale Medien
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  • 82
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The influence of varying doses of streptozotocin and preventive insulin treatment on phospholipid metabolism in sciatic nerve in vitro from diabetic rats was studied. Animals were given 30, 45, and 60 mg/kg injections of streptozotocin and 10 weeks later nerves were removed and incubated in the presence of [32P]orthophosphate. The quantity of isotope incorporated into phosphatidylinositol-4,5-bisphosphate (PIP2) was progressively greater with increasing drug dosage, whereas uptake of label into other phospholipids was unchanged. Rats were made diabetic and within 72 h were implanted with long-acting, insulin-containing osmotic minipumps and the incorporation of [32P]orthophosphate into phospholipids of intact and epineurium-free nerves was examined 8 weeks later. For whole nerve, increased labeling in nerves from diabetic animals occurred only in PIP2 and phosphatidylinositol-4-phosphate (PIP) and was completely prevented by insulin treatment. Isotope incorporation into polyphosphoinositides was also markedly elevated (100%) in desheathed diabetic nerves, but not in nerves from insulin-treated animals. Other phospholipids in epineurium-free nerves displayed some rise in isotope uptake, but the increases were not prevented by insulin treatment and appeared unrelated to hyperglycemia. Morphological examination of nerves extended previous findings that prolonged insulin treatment produces axonal degeneration. These observations indicate that abnormal nerve polyphosphoinositide metabolism is at least in part a consequence of hyperglycemia. The metabolic alterations may be intimately involved in reduced nerve conduction velocity, which is characteristic of diabetic neuropathy.
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  • 83
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: A neuroblastoma × Chinese hamster embryonic brain explant hybrid cell line (NCB-20) expressed 5-hydroxytryptamine (5-HT1) receptors, linked to adenylate cyclase, which closely resembled 5-HT1 receptors previously characterized in central nervous tissue. However, the affinity of the receptors for 5-HT was only 150 nM compared to 5 nM in membranes prepared from cerebral cortex. The elevation of cyclic AMP levels in NCB-20 cells produced by 5-HT was found additive to that produced by cholera toxin but synergistic with that produced by either prostaglandin E1 (PGE1) or forskolin, suggesting that these latter two agents elevate cyclic AMP levels by a different mechanism than 5-HT. The elevation of cyclic AMP levels by either 5-HT or PGE1 was reversed by [D-Ala2,D-Leu5]enkephalin (DADLE), morphine, clonidine, and 3,4-dihydroxyphenylethylamine (dopamine) on a short (30 min) time scale. However, continued exposure to DADLE resulted in loss of the initial inhibitory effects of DADLE after 6 h and return of cyclic AMP levels to that seen with either 5-HT or PGE1 alone. When the DADLE exposure time was increased to 48 h, 5-HT produced a further twofold increase in cyclic AMP levels, but there was no increase in the responsiveness of the cells to PGE1 unless naloxone was added 1 h prior to treatment with PGE1. Scatchard analysis showed that the increased potency of 5-HT resulted from an increase in receptor affinity for 5-HT (from a KD of 150 ± 20 nM to one of 20 ± 7 nM), with a reduction in the number of apparent binding sites. The 5-HT supersensitivity observed in NCB-20 cells may be a good model for neurotransmitter interactions that produce desensitization or facilitation in the intact nervous system.
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  • 84
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Four hybridoma lines secreting monoclonal antibodies to benzodiazepines were produced after BALB/c mice were immunized with a benzodiazepine-bovine serum albumin conjugate. The monoclonal antibodies were purified from ascites fluids, and their binding affinities for benzodiazepines and other benzodiazepine receptor ligands were determined. These antibodies have very high binding affinities for diazepam, flunitrazepam, Ro5-4864, Ro5-3453, Ro11–6896, and Ro5–3438 (the KD values are in the 10−9M range). However, these antibodies have low affinities for the benzodiazepine receptor inverse agonists (β-carbolines) and antagonists (Ro15–1788 and CGS-8216).
    Materialart: Digitale Medien
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  • 85
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The composition of CNS myelin was investigated in rats adrenalectomized at day 14 and killed 7 days later, previously shown to result in a 25% reduction in the amount of bulk-isolated myelin and a 40% decrease in brain glycerol 3-phosphate dehydrogenase activity. The proportions of the major myelin proteins, as well as the specific activity of 2′,3′-cyclic nucleotide 3′-phosphohydrolase, were the same in the myelin from both adrenalectomized and control animals. The amount of total phospholipid and the proportions of individual phospholipids were also normal in myelin from the adrenalectomized animals. The amount of nonmyelin phospholipid in whole brain was unchanged by adrenalectomy. Labeling studies carried out 4 days after adrenalectomy of 14-day-old animals showed no change in the synthesis rates of the major myelin phospholipids as compared with the synthesis rate of nonmyelin phospholipids. Furthermore, incorporation of [1,(3)-14C]glycerol into the glycerol moiety of ethanolamine plasmalogen, which requires glycerol 3-phosphate dehydrogenase, was also normal, showing that the reduced oligodendroglial glycerol 3-phosphate dehydrogenase activity following adrenalectomy was not rate-limiting for myelin phospholipid synthesis.
    Materialart: Digitale Medien
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  • 86
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The binding of [3H]diazepam to cell homogenates of embryonic rat brain neurons grown in culture was examined. Under the conditions used to prepare and maintain these neurons, only a single, saturable, high-affinity binding site was observed. The binding of [3H]diazepam was potently inhibited by the CNS-specific benzodiazepine clonazepam (Ki= 0.56 ± 0.08 nM) but was not affected by the peripheral-type receptor ligand Ro5-4864. The KD for [3H]diazepam bound specifically to cell homogenates was 2.64 ± 0.24 nM, and the Bmax was 952 ± 43 fmol/mg of protein. [3H]Diazepam binding to cell membranes washed three times was stimulated dose-dependently by γ-aminobutyric acid (GABA), reaching 112 ± 7.5% above control values at 10−4M. The rank order for potency of drug binding to the benzodiazepine receptor site in cultured neurons was clonazepam 〉 diazepam 〉 β-carboline-3-carboxylate ethyl ester 〉 Ro15-1788 〉 CL218,872 〉 Ro5-4864. The binding characteristics of this site are very similar to those of the Type II benzodiazepine receptors present in rat brain. These data demonstrate that part, if not all, of the benzodiazepine-GABA-chloride ionophore receptor complex is being expressed by cultured embryonic rat brain neurons in the absence of accompanying glial cells and suggest that these cultures may serve as a model system for the study of Type II benzodiazepine receptor function.
    Materialart: Digitale Medien
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  • 87
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: When indole-3-acetaldehyde was incubated with rat brain tissue, an aldehyde dehydrogenase-independent irreversible disappearance of the aldehyde was found. This was accompanied by an increase in absorbance at 240–400 nm, with a peak at 310 nm. The results suggested that this change in absorbance was caused by a membrane-bound nonenzymatic reaction between indole-3-acetaldehyde and phospholipids. A similar reaction occurred between indole-3-acetaldehyde and pure preparations of phosphatidylethanolamine and phosphatidylserine, but not phosphatidylcholine. Indole-3-acetaldehyde levels also decreased slightly when incubated with albumin but absorbance at 310 nm was unaltered. It is suggested that nonenzymatic reactions between indole-3-acetaldehyde (or other biogenic aldehydes) and membrane components might occur in vivo, and could be involved in the effects of drugs such as ethanol and barbiturates.
    Materialart: Digitale Medien
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  • 88
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: This study evaluated the ability of γ-aminobutyric acid (GABA), baclofen, monovalent anions, divalent cations, and various combinations thereof to protect solubilized benzodiazepine (BZ) receptors of types 1 and 2, when contained together on the complex, against heat inactivation. Neither anions, cations, nor GABA alone provided significant protection of solubilized BZ receptors against heat, but inclusion of monovalent anions or divalent cations together with 500 μM GABA did afford protection. Monovalent anions combined with GABA (500 μM) provided 50% to full protection. Divalent cations, such as CaCl2 (2.5 mM) or MgCl2 (2.5 mM) in the presence of GABA (500 μM) yielded 45% and 24% protection, respectively. Other divalent cations tested (Zn2+, Hg2+, Co2+, and Ni2+) were poor protectors, even when combined with GABA. Monovalent anions (200 mM NaCl) and divalent cations (5 mM CaCl2) when tested together provided no protection. Similarly, baclofen (the GABA-B agonist) provided no protection, either alone or together with anions or divalent cations. These results indicate that the independent but interacting recognition sites of GABA, BZ, anions, and divalent cations, previously detected in the membrane-bound state, are retained in the solubilized state.
    Materialart: Digitale Medien
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  • 89
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Levels of ascorbic acid (AA) in the plasma, brain, and adrenal gland of rats were determined after 15 min of hypoxia (PaO2 〈 25 mm Hg) and following asphyxia. In rabbits, AA plasma levels were followed up to 75 min of reoxygenation following 15 min of hypoxia of the same severity. A significant increase (∼70%) in AA levels was found in plasma of rats and rabbits after hypoxia and asphyxia. This increase was found to be transient, with a return to normal levels within 1 h after resumption of normal oxygenation. Pretreatment with dexamethasone reduced the increase in AA level in both rabbits and rats. Adrenalectomy in rats, performed 24 h before the experiment, abolished the response to hypoxia. Ascorbate levels in the cerebral cortex, hypothalamus, and adrenal gland of awake rats subjected to hypoxia or asphyxia were found to be the same as in normoxic rats. Our results suggest that the observed changes in plasma AA levels are probably mediated through adrenocorticotropic hormone and that the adrenal gland is the major source of ascorbate efflux into the circulation during oxygen deprivation.
    Materialart: Digitale Medien
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  • 90
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Intramuscular administration of methionine to mice resulted in changes in the levels of aspartate, glutamate, glutamine, and γ-aminobutyrate in both nerve endings (synaptosomes) and “non-nerve-ending” tissue in the brain. However, the amino acid changes in the two locations differed considerably, not only in the time to onset of the changes, but also in the direction of the changes and in their duration. The results provide additional support for a glutamate-glutamine cycle between neurons and glia, and suggest that the decreases in amino acid levels in the nerve endings are due to an insufficient supply of glutamine from glia or other cellular structures, possibly compounded by an impairment in the uptake of glutamine into the nerve terminals. The primary cause of the glutamine deficiency is unknown because methionine did not affect the enzymes of glutamate and glutamine metabolism. Treatment of mice with methionine also resulted in an anticonvulsant action, but no correlation was observed between the latter phenomenon and the glutamate content of nerve endings.
    Materialart: Digitale Medien
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  • 91
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: When rat brain synaptosomes were incubated for 10 min at 37°C, basal accumulation of adenosine in the medium was 66 pmol/mg of protein. An elevated K+ level (24 mM) evoked an additional accumulation of 200 pmol/mg of protein, and 50 μM veratridine evoked 583 pmol of adenosine accumulation/mg of protein. K+- and veratridine-evoked accumulation of adenosine did not arise from microsomal or mitochondrial contaminants of the synaptosomal preparation, because purified microsomes and mitochondria did not exhibit evoked accumulation of adenosine in the medium. K+-evoked accumulation of extrasynaptosomal adenosine was Ca2+-dependent, whereas veratridine-evoked accumulation of adenosine was increased in Ca2+-free medium. In the presence of α,β-methylene ADP and GMP, which inhibit ecto-5′-nucleotidase, conversion of added ATP and AMP to adenosine was inhibited by 90% in synaptosomal suspensions. However, inhibition of ecto-5′-nucleotidase only reduced basal extrasynaptosomal accumulation of adenosine by 74%, veratridine-evoked accumulation of adenosine by 46%, and K+-evoked accumulation by 33%. Most of the basal accumulation of extrasynaptosomal adenosine appears to be derived from released nucleotide, probably ATP, but about half of the veratridine-evoked accumulation of adenosine and most of the K+-evoked accumulation may arise from adenosine released in its own right, rather than from a released nucleotide.
    Materialart: Digitale Medien
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  • 92
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Phosphatidyl –N,N - dimethylethanolamine (PDME), an intermediate in the formation of phosphatidylcholine (PC) by the sequential methylation of phosphatidylethanolamine (PE), was purified from rat brain and its fatty acid (FA) composition compared with those of brain PC and PE. The proportion of polyunsaturated fatty acids (PUFAs) in the PDME (29.8%) was similar to that of PE (27.7%) and much greater than in PC (2.8%). Like the PUFAs of PE, the major PUFAs found in PDME were arachidonic acid (20:4) and docosahexaenoic acid (22:6). An isotopic method was developed to quantify the PDME purified from brain; a tritiated methyl group from CH3I was transferred to the PDME in the presence of cyclohexylamine to form [3H]PC, and the radioactivity of the PC was then counted. The concentration of rat brain PDME obtained using this method (33.0 ± 1.8 μg/g brain) was very similar to that obtained using quantitative GLC analysis of its FAs (36.9 ± 1.8 μg/g). The FAs in the PE and PC of rat brain synaptosomes were also analyzed; too little PDME was present in synaptosomes to permit similar analysis. The percentage of unsaturated FAs insynaptosomal PE was even higher (43.4 vs. 27.7) than that in PE prepared from whole brain. Since synaptosomes have a very high activity of phosphatidyl-N-methyltransferase, the enzyme complex that methylates PE to form PC, this enzyme may serve, in nerve endings, to produce a particular pool of PC, rich in PUFAs, which may have a distinct physiological function.
    Materialart: Digitale Medien
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  • 93
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 45 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: [3H]γ-Hydroxybutyric acid ([3H]GHB) at physiological concentration incubated with brain slices in Krebs-Ringer medium produced [3H]γ-aminobutyric acid ([3H]GABA). This compound was identified by its Rf values on thin-layer chromatograms and by analysis of the dansyl derivatives of the free amino acid fraction. No labelled glutamate could be detected. Brain slices incubated with labelled glutamate and nonradioactive GHB generated labelled 2-oxoglutarate, suggesting that γ-aminobutyrate-2-oxoglutarate transaminase (GABA-T) is involved in catalyzing this reaction. Furthermore, specific inhibitors of GABA-T blocked the production of labelled GABA from labelled GHB and of labelled 2-oxoglutarate from labelled glutamate. Transformation of [3H]GHB into [3H]GABA was not inhibited by malonate, demonstrating that the succinate-linked pathway is not involved in the generation of GABA. The kinetic characteristics of the multienzyme system involved in GHB degradation studied in vitro are compatible with the production of GABA in vivo.
    Materialart: Digitale Medien
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  • 94
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 44 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: This study attempts to determine if L-glutamate and/or L-aspartate may be transmitters of neural tracts descending from the brain to the spinal cord. The uptake and electrically evoked release of D-[3H]aspartate, a putative marker for L-glutamate and L-aspartate, were measured in the cervical enlargement of the guinea pig spinal cord. These activities were compared using unlesioned animals and others with a lesion on the right side of the spinal cord. Partial cordotomy (segment C5) produced a heavy loss of descending fibers, a small loss of primary sensory fibers, and a depression of the uptake and the Ca2+-dependent, electrically evoked release of D-aspartate ipsilateral and caudal to the lesion. Contralaterally, there was a moderate loss of corticospinal fibers, some loss of other descending axons, and a depression of D-aspartate release. Dorsal rhizotomy (segments C4–T1) produced a heavy loss of primary sensory fibers ipsilateral to the lesion. Ipsilaterally, but not contralaterally, the uptake and release of D-aspartate were depressed. Degeneration after partial cordotomy in combination with dorsal rhizotomy was assumed to be the sum of that produced by each lesion separately. This combined lesion depressed D-aspartate uptake ipsilaterally and depressed D-aspartate release on both sides of the cervical enlargement. None of the lesions altered the up-take and the evoked release of [3H]GABA. These findings support the hypothesis that the synaptic endings of one or more neural tracts descending from the brain to the spinal cord mediate the uptake and release of D-aspartate and, therefore, may use L-glutamate or L-aspartate as a transmitter.
    Materialart: Digitale Medien
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  • 95
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 44 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Nipecotic acid has been demonstrated to block the γ-aminobutyric acid transport systems. Previous studies have shown that the uptake system is the first transmitter-specific parameter to appear during the development of the rabbit retina. Use of these observations has been made to study the influence on the development of γ-aminobutyric acid receptors of altering the uptake mechanism by treating newborn pups with nipecotic acid to block GABA transport. The present study of the in vivo metabolism of [3H]nipecotic acid in the CNS measured the changes in the levels of [3H]nipecotic acid in both adult and newborn rabbit retinas after injection of the label into the vitreal chamber. It was found that the effective half-life of [3H]nipecotic acid in the vitreous is about 5 h for adult tissue and 3 h for newborn. In contrast, all retinal fractions retained the label longer, the effective half-lives being about 60 h (adult) and 45 h (newborn). Further, no labeled metabolites of nipecotic acid were detected in either adult or newborn tissue. This study gives evidence that the degradation of nipecotic acid in nervous tissue is minimal and suggests that, although the rate of clearance is faster in neonates, the fate of nipecotic acid in vivo may be similar in both adult and newborn tissues.
    Materialart: Digitale Medien
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  • 96
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 44 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: [3H]Flunitrazepam (FNP) and [3H]methyl β-carboline-3-carboxylate (MCC) binding was examined in soluble and particulate fractions from membranes solubilized with Triton X-100 or in subfractions of synaptosomal membranes obtained by a physical separation technique. Results using both methods demonstrate that benzodiazepine and β-carboline sites reside on both pre- and postsynaptic membranes. Further, subfractionation experiments indicate that the binding sites for both ligands are unequally distributed within the synapse and among brain regions. For example, in cerebral cortical presynaptic membranes there are twice as many FNP as MCC sites whereas in postsynaptic membranes this ratio is reversed. The number of FNP and MCC sites are equal in the presynaptic fraction from cerebellum. The postsynaptic membranes derived from cerebellum have three times the number of FNP compared to MCC sites. In hippocampus this ratio varies between 1.5 and 2.8 in each subfraction. These results support the idea that benzodiazepine and β-carboline binding sites represent different recognition sites.
    Materialart: Digitale Medien
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  • 97
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 44 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Chromaffin granules, the catecholaminergic storage granules from adrenal chromaffin cells, lysed in 10−9–10−7M Fe2+. Lysis was accompanied by the production of malondialdehyde which results from lipid peroxidation. Both chromaffin granule lysis and malondialdehyde production were inhibited by the free radical trapping agent butylated hydroxytoluene but not by catalase and/or superoxide dismutase. The results suggest that lysis resulted from a direct transfer of electrons from Fe2+ to a component of the chromaffin granule membrane without the participation of either superoxide or hydrogen peroxide and may have resulted from lipid peroxidation. In some experiments, ascorbate alone induced chromaffin granule lysis which was inhibited by EDTA, EGTA, or deferoxamine. The lysis was probably caused by trace amounts of reducible polyvalent cation. Lysis sometimes occurred when Ca2+ was added with EGTA (10 μM free Ca2+ concentration) and was consistently observed together with malondialdehyde production in the presence of Ca2+, EGTA, and 10 μM Fe2+ (total concentration). The apparent Ca2+ dependency for chromaffin granule lysis and malondialdehyde production was probably caused by a trace reducible polyvalent ion displaced by Ca2+ from EGTA and not by a Ca2+-dependent reaction involving the chromaffin granule.
    Materialart: Digitale Medien
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  • 98
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 44 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Differences in binding properties of μ and δ opioid receptors were investigated using DAGO (Tyr-d-Ala-Gly-MePhe-Gly-ol) and DTLET (Tyr-d-Thr-Gly-Phe-Leu-Thr), which occur, respectively, as the most selective μ and δ radioligands available. At high concentration, each agonist is able to interact with its nonspecific sites. Competition experiments indicated that a two-site competitive model was adequate to explain the interactions of DAGO and DTLET with [3H]DTLET and [3H]DAGO binding sites, respectively. The weak cross-reactivity (≃10%) of DTLET for μ sites was taken into account in these experiments. On the other hand, DAGO and DTLET exhibit differential binding kinetics. Thus, at 35°C, the lifetime of DTLET within its receptor site about 14 times longer than that of the μ agonist. Sodium and manganese ions decrease the maximal number of high affinity μ and δ sites, but the sensitivity of μ receptors is three times higher towards Na+ and 20-fold higher towards Mn2+ than that of δ receptors. GTP reduces similarly the μ and δ binding whereas only the DAGO binding was modified by the nonhydrolyzable analogue guanylylimidodiphosphate [GMP-P(NH)P]. However, in the presence of Na+ ions, GMP-P(NH)P inhibits the DTLET binding in a concentration-dependent manner. The effects of Na+ and GMP-P(NH)P could be explained by a sequential transformation of δ receptors to low-affinity states. This model predicts that Na+, by lowering the affinity of a fraction of sites, produces a decrease in the maximal number of high-affinity δ receptors and that GMP-P(NH)P enhances the Na+, effect. Moreover, the binding kinetic to this high-affinity state was also modified by Na+ and nucleotides. All of these data support the existence of two independent μ and δ binding sites, the properties of which are differentially regulated by these endogenous effectors.
    Materialart: Digitale Medien
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  • 99
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 44 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The synthesis of purine nucleotides from the salvage precursors adenine and adenosine, and from the de novo precursors formate and glycine, was studied in isolated adrenal chromaffin cells. Both [8-14C]adenine and [8-14C]adenosine from extracellular medium are effectively incorporated into intracellular nucleotides. [14C]Formate and [U-14C]glycine are also incorporated, but de novo synthesis is clearly lower than synthesis from salvage precursors, although similar to de novo synthesis in liver. The enzymes responsible for adenine and adenosine salvage, adenine phosphoribosyltransferase and adenosine kinase, were purified about 1,500-fold. Both enzymes are mainly cytosolic and exhibit a similar molecular weight of around 42,000. The results suggest that chromaffin cells can replenish their intracellular nucleotides lost during the secretory event by an active synthesis from salvage and de novo precursors.
    Materialart: Digitale Medien
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  • 100
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 44 (1985), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: The metabolism of 3,4-dihydroxyphenylethylamine (DA, dopamine) and norepinephrine (NE) both normally, and after the administration of levo-3,4-dihydroxyphenylalanine (l-DOPA), has been studied in several regions of the developing spinal cord of the rat from fetal day (FD) 16 to the young adult stage. During late fetal (from FD 16) and most of neonatal life [to neonatal day (ND) 20], dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were either just detectable or present in very low concentration in all regions in the untreated developing rat. However, the developing spinal cord possesses an enormous capacity to metabolize the large amounts of DA synthesized from injected l-DOPA. At the end of 1 h after 100 mg/kg i.p. of l-DOPA, DOPAC and HVA are 54 ± 14 (n = 5) and 16 ± 5 (n = 5) nmol/g, respectively, in the thoracic zona intermedia in the 12h-old (ND 0.5) rat. This metabolic capability is already highly developed as early as FD 16, peaks during the first half of neonatal life (ND 4 for DOPAC, and ND 15 for HVA), and is considerably reduced toward the end of neonatal life (approximately ND 28) and in the young adult. Control experiments suggest that a substantial part of this synthesis (from l-DOPA) and metabolism of DA occurs in elements other than the descending monoaminergic nerve fibers. By comparison, the synthesis and metabolism of NE develop more slowly, peak in the latter half of neonatal life, and then decline to the level found in the young adult. In the ventral horn of the lumbar region, however, the capacity to metabolize NE develops more rapidly than in the dorsal horn and zona intermedia. The results suggest that the activities of several enzymes involved in the synthesis (aromatic amino acid decarboxylase) and inactivation of catecholamines (monoamine oxidase and catechol-O-methyltransferase) are already highly developed by FD 16, and achieve their highest activities in the spinal cord during early neonatal life.
    Materialart: Digitale Medien
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