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Effects of SCH 32651 on resting and stimulated acid secretion in guinea‐pig isolated fundic mucosa
Author(s) -
Barnett Allen,
Chiu Peter J.S.,
Tetzloff Glen
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb10121.x
Subject(s) - cimetidine , histamine , theophylline , methacholine , endocrinology , medicine , secretion , gastric acid , chemistry , atropine , ouabain , guinea pig , biology , sodium , respiratory disease , organic chemistry , lung
1 Effects of SCH 32651, a novel antisecretory and cytoprotective agent, on resting and stimulated acid secretion by the guinea‐pig isolated fundic mucosa were studied. 2 SCH 32651 inhibited resting acid secretion in proportion to concentrations in serosal solution (0.1–10 μ m ), the IC 50 being 4.4 μ m . Cimetidine and atropine at concentrations up to 100 μ m were inactive. 3 Serosal application of SCH 32651 inhibited acid secretory responses to histamine (10 μ m ), methacholine (1 μ m ) or dibutyryl cyclic AMP (0.5 m m ) plus theophylline (1 m m ) in a concentration‐dependent manner. The IC 50 s against histamine, methacholine and db cyclic AMP plus theophylline were 4.2 μ m , 0.71 μ m and 2.9 μ m , respectively. In contrast, atropine and cimetidine each at 100 μ m , a concentration that entirely abolished responses to methacholine and histamine, respectively, did not affect acid responses to db cyclic AMP plus theophylline. 4 The inhibitory effects of SCH 32651 on resting and histamine‐stimulated acid secretion were readily reversible upon washing. 5 SCH 32651 0.1 m m in the mucosal solution also greatly suppressed the resting and stimulated acid secretion. 6 In the presence of histamine treatment, SCH 32651 concomitantly caused a marked rise in K + entry into the mucosal solution in parallel to a decline in the appearance of H + in the same solution. 7 The various events demonstrated by SCH 32651 in the present study are shared by omeprazole, a potent antisecretory agent working through inhibition of gastric H + /K + ‐ATPase. We conclude that SCH 32651 as a potent antisecretory agent seems to act directly on the parietal cell, near or at the site of H + /K + ‐ATPase which is a final step in the acid secretory process triggered by various stimuli.