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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 6 (1979), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Effects of epinine on cyclic AMP and contractility were investigated in rabbit papillary muscles driven at a rate of 0.5 or 2.0 Hz.2. When the frequency of stimulation was increased from 0.5 to 2.0 Hz, the log dose-response curve for the positive inotropic effect of epinine was displaced to the left, whereas the maximum of the developed tension was not changed.3. At both frequencies phentolamine (1 μmol/1) shifted the lower part of the log dose-response curve for epinine to the right, whereas pindolol (30 nmol/1) affected mainly the upper part. In the presence of both a- and β-adrenoceptor antagonists, the whole curve was shifted to the right in a parallel manner. However, cocaine (30 μmol/1) did not significantly influence the log dose-response curve of epinine.4. At 0.5 Hz a submaximal effective concentration of epinine (100 μmol/1) led to an approximately 100% increase of the cyclic AMP level after 60 s; the same increase of the cyclic AMP level was induced at 2.0 Hz by one-third the concentration of epinine (30 μmol/1).5. Phentolamine (1 μmol/1) did not affect the increase of the cyclic AMP level evoked by epinine, whereas pindolol (30 μmol/1) completely depressed it.6. The present results indicate that epinine produces its positive inotropic effect through direct stimulation of myocardial α-adrenoceptors as well as β-adrenoceptors, depending upon the concentration: in lower concentrations it acts mainly on α-adrenoceptors, whereas in higher concentrations it acts predominantly on β-adrenoceptors. The positive inotropic effect through α-adrenoceptor stimulation is mediated by cyclic AMP, while that through a-adrenoceptors is not.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 29 (1973), S. 339-339 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 102 (1981), S. 49-55 
    ISSN: 1432-1335
    Keywords: KMOE cells ; Erythroid cells ; Human cell line ; Erythroid differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Three continuous human cell lines, designated KMOE, derived from a patient with acute erythremia (Di Guglielmo's disease) are reported. The cell lines are the cultures of (1) bone marrow cells, (2) peripheral blood cells, and (3) cells from a tumor developed into an athymic nude mouse after transplantation of the cultured bone marrow cells. Cells of all three lines show morphology of immature erythroblast and have i(17q) marker chromosome. They are negative for both Philadelphia chromosome and Epstein-Barr virus nuclear antigen. Although all KMOE cells in suspension culture are benzidine-negative, benzidine-positive cells are found within colonies formed in semi-solid culture media. The relative number of colonies with benzidine-positive cells is increased when sodium butyrate is added to the culture. The KMOE cell lines are human erythroid cell lines with erythroblastic morphology and still retain their tendency for differentiation.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: Nicardipine Grapefruit juice Intestinal drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract. Objectives: To assess relative roles of the intestinal and hepatic stereoselective metabolism of nicardipine in an oral first-pass disposal with and without grapefruit juice intake. Methods: The kinetic profiles of (+)- and (–)-nicardipine were studied in the six normal healthy male volunteers who received oral (40 mg) and intravenous (2 mg) racemic nicardipine, first with water and second with grapefruit juice. Both the enantiomers were determined by the stereoselective high-performance liquid chromatographic method, and hemodynamic parameters (arterial blood pressure, heart rate, and electrocardiogram) were assessed when each blood sample was taken. Results: Grapefruit juice compared with water intake caused a significant (P〈0.05) increase in the mean oral (+)- and (–)-nicardipine bioavailability (Fobs) (48.6±5.0% and 105.6±7.8%) and dose-absorbed (Fabs) available fraction unmetabolized at the gut (Fg) (48.2±5.6% and 110.9±8.8%, respectively) with no significant change in the hepatic first-pass effect. However, all of the mean kinetic parameters of both the enantiomers after the intravenous dosing of racemic nicardipine did not differ between the grapefruit juice- and water-intake trial phases. The mean percentage changes in oral AUC (43.1±3.4% in [+]-nicardipine and 90.9±6.4% in [–]-nicardipine, or Fobs) and Fabs·Fg by grapefruit juice tended to be greater for (–)-nicardipine than for (+)-nicardipine and the mean oral (+)/(–)-nicardipine AUC ratio was significantly reduced by grapefruit juice (from 2.25±0.37 to 1.75±0.28) (P〈0.05). Except for heart rates, which were greater with grapefruit juice (P〈0.05) at 1 and 2 h after the oral dose of nicardipine, the mean hemodynamic variables did not differ between the two trial phases. Conclusion: We conclude that the gut is the major presystemic disposal site of racemic nicardipine in humans. Grapefruit juice appears to affect this metabolic disposal of (–)-nicardipine to a somewhat greater extent compared with that of (+)-nicardipine, with an early postdose transient tachycardia after the oral dosing of racemic nicardipine.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1912
    Keywords: Dopamine ; Contractility ; Papillary muscle ; α- and β-adrenoceptors ; Cyclic AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the isolated rabbit papillary muscle the effects of dopamine on the contractile force and on the level of 3′,5′-cyclic adenosine monophosphate (cAMP) at different frequencies of stimulation were studied and compared with those of isoprenaline and adrenaline. 1. When the frequency of stimulation was increased from 0.5–2.5 Hz the dose-response curves for the positive inotropic effect of dopamine as well as of isoprenaline were shifted to the left, whereas the maximum of the developed tension reached for both drugs remained unchanged. 2. At a frequency of stimulation of 0.5 Hz pindolol (3×10−8 M) and phentolamine (10−6 M), respectively, did not affect the dose-response curve for dopamine; only the simultaneous administration of pindolol plus phentolamine shifted the dose-response curve to the right. In the presence of cocaine (3×10−5 M) as well as in that of cocaine plus corticosterone (4×10−5 M) the dose-response curve for dopamine was shifted to the right. On the other hand, the upper part of the dose-response curve for adrenaline was shifted to the right by pindolol (3×10−8 M), the lower part by phentolamine (10−6 M) and the whole curve by the application of both antagonists. 3. At a frequency of stimulation of 2.5 Hz neither pindolol (3×10−8 M) nor phetolamine (10−6 M) influenced the dose-response curve for dopamine, whereas the simultaneous administration of both drugs shifted the whole curve to the right. 4. Dopamine (10−4 M) increased significantly the content of the cAMP after 60 s by about 40% (at 0.5 Hz) and 50% (at 1.0 Hz), respectively, but this increase was by far less compared with that obtained by isoprenaline (3×10−7 M). 5. Pindolol (3×10−8 M) completely abolished the increase of the cAMP-content evoked by dopamine (10−4 M), while phentolamine (10−6 M) enhanced the elevation of the cAMP-level to nearly the same extent as isoprenaline (3×10−7 M) did. 6. The increase of the cAMP level induced by adrenaline (10−5 M) was comparable with that caused by isoprenaline (3×10−7 M). While phentolamine (10−6 M) did not influence the adrenaline induced increase of the cAMP content, pindolol completely abolished it. 7. The present results are compatible with the view, that the positive inotropic effect via stimulation of β-adrenoceptors is mediated by cAMP, while that of α-adrenoceptors is not. Furthermore it is concluded, that dopamine produces its positive inotropic effect by a cAMP-dependent direct and/or indirect β-adrenoceptor stimulation as well as by a cAMP-independent direct α-adrenoceptor stimulation to about the same degree.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 341 (1990), S. 14-21 
    ISSN: 1432-1912
    Keywords: Human cardiac muscarinic cholinoceptors ; Muscarinic cholinoceptor subtypes ; Human right atrium ; Human left papillary muscle ; Negative inotropic effect ; [N-Methyl-3H]-scopolamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In human atrial and ventricular myocardium, the muscarinic cholinoceptor (M-cholinoceptor) populations were characterized by means of radioligand binding (with [N-methyl-3H]-scopolamine ([3H]-NMS) as the ligand) and functional experiments (negative inotropic effect of carbachol on isolated electrically driven right atrial and left papillary muscle preparations). (1) Binding of [3H]-NMS to human atrial and ventricular membranes was rapid, reversible and saturable (KD-values: 0.5–1.0 nmol/l). The maximal number of [3H]-NMS binding sites, however, was approximately 2.5-fold higher in right and left atrial membranes (200–250 fmol[3H]-NMS specifically bound/mg protein) than in right and left ventricular membranes (80–100 fmol/mg protein). (2) M-cholinoceptor antagonists inhibited [3H]-NMS binding to right atrial and left ventricular membranes with steep, monophasic competition curves indicating interaction with a single class of binding sites. In both tissues the order of potency was: atropine 〉 AF-DX 116 〉 hexahydro-siladifenidol (HHSiD) 〉 pirenzepine. (4) It is concluded that, in the human heart, functional M-cholinoceptors mediating negative inotropic effects exist that belong predominantly (if not exclusively) to the M2-subtype. However, the atrial regions of the human heart are more densely endowed with these M2-cholinoceptors than the ventricular myocardium.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1434-601X
    Keywords: PACS: 23.20.Lv Gamma transitions and level energies – 27.70.+q 150 ≤ A ≤ 189
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: High-spin states of 155Gd were populated by using the 154Sm(α,3nγ)155Gd reaction at E α= 33 MeV. γ-γ coincidence, E γ singles, excitation function, and the DCO ratios were measured. we have identified three intermediate bands with ΔI= 2 feeding the positive yrast band. The bands are interpreted as such candidate bands that are mixed with the negative-parity ground state band. This observation can provide a plausible explanation for unusually large population of the positive-parity yrast band observed in a recent Coulomb excitation.
    Type of Medium: Electronic Resource
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