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  • Title: Inhibition of the histamine-stimulated adenylate cyclase activity of guinea pig gastric cells by the H2-receptor antagonists cimetidine, oxmetidine and SKF 93479.
    Author: Cheret AM, Scarpignato C, Lewin MJ, Bertaccini G.
    Journal: Pharmacology; 1984; 28(5):268-74. PubMed ID: 6728900.
    Abstract:
    The effect of cimetidine and two new histamine H2-receptor antagonists, oxmetidine and SKF 93479, on histamine-stimulated adenylate cyclase activity was studied in guinea pig gastric mucosal cells. Histamine stimulated the enzyme activity in concentration-dependent fashion. The concentration-response curve of histamine was progressively shifted to the right in the presence of increasing concentrations of each antagonist. The Schild plot gave a straight line for all three compounds, with a slope not significantly different from unity and this suggested a competitive antagonism. The calculated pA2 values were 8.45 +/- 0.20, 7.73 +/- 0.21 and 6.81 +/- 0.15 for SKF 93479, oxmetidine and cimetidine, respectively. These results are in accordance with the pharmacological potencies of the antagonists reported on isolated heart preparation and on gastric secretion in vivo. Therefore, the inhibition of histamine-sensitive adenylate cyclase of gastric cells may represent an additional tool for the in vitro evaluation of the H2-receptor antagonists.
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