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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract For the oxyntic cell of the stomach the hypothesis was forwarded by Grossmann and Konturek [1] that, if one of its three receptors is blocked, the physico-chemical properties of the two others are changed in such a way that they respond less sensitively to their specific stimulation. This hypothesis was tested for the heart by studying the effect of histamine-H2-receptor- and β-receptor-blockade on the orciprenaline-, histamine-, and prostaglandin E1-stimulated frequency of the spontaneously beating isolated guinea-pig atrium. Therefore cumulative dose response curves were established for orciprenaline, histamine and prostaglandin E1 (PGE1) alone or in the presence of metiamide or pindolol. (1) The β-blocker pindolol inhibited the effect of orciprenaline in a competitive manner, without having an effect on histamine- and PGE1-stimulation. (2) The histamine H2-receptor blocker metiamide inhibited the histamine response competitively. (3) In contrast to pindolol, metiamide inhibited the PGE1-stimulated rise in atrial frequency, most obviously non- or uncompetitively. From these results it is evident that in the heart the particular inhibitors, at least at the receptor site, act rather specifically without affecting neighbouring receptors and that metiamide influences the PGE1-response in a way different from the receptor site.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 11 (1981), S. 223-227 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 3H-Histamine binding, uptake and metabolism were investigated in intact isolated and enriched parietal cells from the dog and guinea pig. Histamine uptake was sodium dependent and followed by intracellular metabolism. The only metabolite that was detected and extracted from cytosol has been identified by TLC to beN r-methylhistamine. The histamineN-methyltransferase activity appeared to be sodium dependent and was inhibited by mepyramine and chlorpromazine, and also by higher concentrations (10−4–10−3 mol/l) of cimetidine. Two blockers of the sodium channel, amiloride and aminoguanidine, also reduced the enzyme activity by an as yet unknown mechanism.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 60 (1982), S. 1046-1047 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1440
    Keywords: Magenschleimhaut ; Adenylat-Cyclase ; Histamin ; Gastritis ; Ulcus ; Gastric mucosa ; Adenylate cyclase ; Histamine ; Gastritis ; Ulcer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In morphologically different biopsy specimens from fundic, antral and duodenal mucosa of 134 persons, basal and histamine stimulated adenylate cyclase activity was studied: Basal and stimulated adenylate cyclase activities were log-normally distributed. Only in the fundic but not in the antral and duodenal mucosa adenylate cyclase was sensitive to histamine. The mean basal activity in the fundic gastric mucosa was 148, in response to 10−5 mol/l histamine 292 pmol cAMP/mg protein/20 min. In human fundic biopsy specimens histologically identified as normal gastric mucosa, the stimulatory effect of histamine on adenylate cyclase decreased with the individual's age. In bioptic material from patients suffering from histologically proven chronic gastritis the histamine effect decreased with the degree of atrophy. A similar loss of histamine sensitivity was found in gastric mucosal biopsies of antrectomized individuals operated at least 5 years before by the Billroth I or II method, whereas in the mucosa of patients with gastric or duodenal ulcer no loss occurred. In contrast, the most pronounced stimulatory action of histamine was found in this latter group. Since a histamine sensitive adenylate cyclase is localized only in the glandular area of the fundic mucosa and the histamine sensitivity depends on a morphological intact structure of the mucosa, it can be concluded, that the effects of histamine on adenylate cyclase and on hydrochloric acid secretion have to be considered as a mechanism linked together.
    Notes: Zusammenfassung In morphologisch unterschiedlichen Biopsieproben aus der Fundus-, Antrum- und Duodenalschleimhaut von insgesamt 134 Personen wurde die basale und histaminstimulierte Adenylat-Cyclaseaktivität untersucht. Basale und stimulierte Adenylat-Cyclaseaktivität der Schleimhaut des oberen Gastrointestinaltrakts war log-normal verteilt. Nur die Adenylat-Cyclase der Fundusschleimhaut, nicht dagegen die der Antrum- und Duodenalschleimhaut war durch Histamin stimulierbar. In der Fundusschleimhaut betrug die basale Aktivität im Mittel 148, in Gegenwart von 10−5 mol/l Histamin 292 pmol cAMP/mg Protein/20 min. Die Stimulierbarkeit der Adenylat-Cyclase nahm in histologisch gesichert normaler Fundusschleimhaut mit dem Alter und im Biopsiematerial von Patienten mit histologisch diagnostizierter verschiedengradig chronischer Gastritis mit zunehmender Schleimhautatrophie ab. Die Stimulierbarkeit der Adenylat-Cyclase der Fundusschleimhaut durch Histamin war bei Patienten mit einem Magen- oder Duodenalulcus nicht signifikant von der des Normalkollektivs verschieden, obwohl in der Gruppe Duodenalulcus die höchsten Werte gefunden wurden. Demgegenüber war bei Patienten mit 2/3-Resektion nach Billroth I und II die Wirkung von Histamin auf die Enzymaktivität eindeutig vermindert. Da eine histamin-empfindliche Adenylat-Cyclase nur im sekretorischen Anteil des Magens nachweisbar ist und dieser Effekt einer morphologisch intakten Schleimhaut bedarf, lassen die hier vorliegenden Befunde darauf schließen, daß die Wirkungen von Histamin auf Adenylat-Cyclase und Säuresekretion zusammengehörige Vorgänge sind.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: Ciclosporin ; Liver transplantation ; metabolites ; cholestasis ; rejection ; M19 ; M1A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pattern of metabolites of ciclosporin in blood and 24 h-urine of 58 liver graft recipients was routinely monitored by HPLC from transplantation until discharge from hospital. Liver function and ciclosporin metabolite pattern in patients with an uncomplicated clinical course and in those with cholestasis or acute rejection were compared. During cholestasis M19 and M1A, and during acute rejection M19, in blood were significantly elevated compared to the control group. Blood M19 was significantly correlated with bilirubin concentration and γ-glutamyl transferase activity in serum, and M1A with the serum bilirubin concentration. Analysis of the metabolite pattern over the observation period showed higher concentrations of M19 and M1A in blood from patients with cholestasis and acute rejection than in the control group; concentrations were lower in the rejection group than in the cholestasis group. The metabolite pattern in 24 h-urine showed similar alterations in ciclosporin metabolite pattern to those in blood. Cholestasis and rejection shift the ciclosporin metabolite pattern in blood and urine to higher concentrations of M19 and M1A, whereas the concentrations of other metabolites and ciclosporin were not significantly affected.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1041
    Keywords: peptic ulcer ; adenylate cyclase ; cimetidine ; histamine H2-receptor ; histamine H1-receptor ; human gastric mucosa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Biopsy specimens of human fundic mucosa from 96 subjects were assayed for adenylate cyclase activity to characterize specificity of the histamine receptor with selective agonists and antagonists in vitro, and to study the effect of cimetidine therapy. Histamine and the selective histamine H2-receptor agonist dimaprit were almost equally potent throughout the concentration-response curve (10−7–10−3 mol/l); maximal stimulation was obtained with concentrations of 10−4–10−3 mol/l, and half maximal stimulation with about 10−5 mol/l. The selective H1-receptor agonist PEA 10−5 and 10−3 mol/l failed to stimulate adenylate cyclase. Mepyramine 10−6 mol/l, a selective H1-receptor antagonist, and cimetidine 10−6 mol/l, a selective H2-receptor antagonist, did not affect basal adenylate cyclase activity. Histamine-stimulated adenylate cyclase was inhibited in a concentration dependent manner by cimetidine 10−7 and 10−5 mol/l, but not by the same concentrations of mepyramine. Almost identical basal adenylate cyclase activities of about 150 pmol cAMP/mg protein/20 min were found in gastric mucosal biopsies from controls and from peptic ulcer patients, whether or not treated with cimetidine. Histamine 10−5 mol/l doubled adenylate cyclase activity in the controls and the untreated ulcer group, but was completely ineffective in specimens from the cimetidine-treated peptic ulcer patients. The data underline the concept that the effects of histamine on acid secretion and on adenylate cyclase activity are linked together and that the therapeutic effect of cimetidine in ulcer treatment is related to histamine H2-receptor blockade followed by inhibition of adenylate cyclase.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1041
    Keywords: Ciclosporin liver transplantation ; metabolites ; nephrotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Blood ciclosporin (Cs) metabolite pattern in 58 liver grafted patients was routinely monitored by HPLC from the first Cs dose after transplantation until discharge from hospital. Eighteen patients with normal kidney function were allocated to Group I and 14 patients in Group II suffered Cs nephrotoxicity during their clinical course. There were no significant differences between both groups in blood Cs level, kidney function before transplantation, liver function or co-administration of other potentially nephrotoxic drugs. A correlation matrix involving both groups showed a significant correlation between the blood concentration of metabolite M1c9 and serum creatinine and urea, and an inverse correlation with creatinine clearance. During a nephrotoxic episode the blood concentrations of metabolites M1c9 and M1A were significantly elevated in patients in Group II. Analysis of the time course revealed significantly higher blood levels of M19 and M1c9 in Group II patients compared with those in Group I for the first 10 days after transplantation. Serum creatinine and urea concentrations remained significantly elevated, the creatinine clearance being significantly reduced throughout the period of observation. The elevated blood concentrations of ciclosporin metabolites M1c9 and M19 during nephrotoxic episodes suggest that these metabolites are associated with ciclosporin nephrotoxicity. It could not be decided if the elevated metabolite concentrations were the result of and/or the reason for impaired kidney function.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 4 (1990), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We studied the effects of prostaglandin (PG) E2, carbenoxolone, cholecystokinin-octapeptide (CCK-OP), and the thromboxane-mimetic U46619, all known to stimulate gastric mucus secretion in vivo, on protein and glycoprotein synthesis in and release from isolated and enriched pig gastric mucous cells, as measured by the incorporation of [3H]L-leucine and N-acetyl-[14C]D-glucosamine respectively into cellular and released acid insoluble material. PGE2 stimulated glycoprotein and protein synthesis (EC50 7 and 30 nmol/L, respectively) and release (EC50 50 and 140 nmol/L, respectively) in a concentration-dependent manner, whereas carbenoxolone, CCK-OP and U46619 failed to enhance the incorporation of the tracers. We conclude that stimulation of mucus secretion by PGE2 is related to direct effects on protein and glycoprotein production of gastric non-parietal cells, whereas indirect effects may be involved in the stimulation by carbenoxolone, CCK-OP, and U46619.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 4 (1990), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Alimentary pharmacology & therapeutics 1 (1987), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The antisecretory action of the antidepressant drugs trimipramine, doxepin and nortriptyline was studied in two different in-vitro test systems; the isolated and enriched guinea-pig parietal cell and the purified H+/K+-ATPase preparation. The effect of the antidepressants was compared with that of the neuroleptic agents chlorpromazine, triflupromazine, trifluoperazine, haloperidol, fluspirilene and with that of the tricyclic anticholinergic agent pirenzepine. All neuroleptics and antidepressants inhibited acid formation in intact parietal cells with IC50 values in the nanomolar range. The inhibitory potency for each compound was identical regardless of whether histamine or db-cAMP was used as stimulant. Isolated H+/K+-ATPase, measured in the presence of 5 mmol litre−1 KCl, was inhibited by all psychotropic drugs with IC50 values in the micromolar range. EGTA did not affect the inhibitory potency at the H+/K+-ATPase, indicating that the action of the drugs does not depend on their calmodulin blocking activity. Pirenzepine was ineffective in both test systems. Kinetic studies done with nortriptyline, chlorpromazine and haloperidol showed a competitive type of inhibition with respect to K+ at low inhibitor concentrations. This competitive type was changed to a mixed type of inhibition with increasing inhibitor concentrations, demonstrating cooperative effects between drug binding and K+ activation of the enzyme. From these data it is suggested that antidepressants and neuroleptics act by an allosteric mechanism of action, and that the lipid solubility is a significant factor to establish enzyme inhibition.
    Type of Medium: Electronic Resource
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