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Comparison of cimetidine with new H2-antagonists in rabbit and guinea pig gastric cells.
S Batzri; J W Harmon; R Toles (Profiled Author: John Harmon)
European journal of pharmacology 1983;94(1-2):1-8.Abstract
We compared the effect of three relatively new H2-antagonists (compounds L-643,411, BL-6341A and SK&F 93479) to cimetidine in two preparations of mucosal cells isolated from rabbit and guinea pig stomachs. The indices for the histamine-stimulated acid secretory response were the changes in [14C]aminopyrine uptake in the rabbit and in cellular cyclic AMP, in the guinea pig. Both functions were mediated by the histamine H2-receptors and hence, can be used to examine antagonist-receptor interaction in vitro. In both rabbit and guinea pig, the new antagonists were highly potent competitive inhibitors of histamine on the H2-receptor, 30- to 200-fold more potent than cimetidine. The Ki values for cimetidine (500-800 nM) and L-643,411 (6-12 nM) were the same in the two animal species, but those for SK&F 93479 and BL-6431A were significantly lower in rabbit than in guinea pig cells. In inhibiting the changes in [14C]aminopyrine uptake in rabbit cells the Ki values for SK&F 93479 and BL-6341A were 2.4-3.5 nM whereas on cyclic AMP in guinea pig cells they were 10-fold higher (25-30 nM). These differences may reflect the structural requirements of the H2-receptors in that in rabbit these antagonists possess higher affinity for the H2-receptors than in guinea pig, or alternatively, uptake or metabolism of histamine by rabbit gastric cells may be responsible for these differences. Furthermore, these preparations appeared to be satisfactory for in vitro assay of gastric acid secretion to test for competitiveness of new H2-receptor antagonists.
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