Effects of topical application of acidified omeprazole on acid secretion and transmucosal potential difference in anesthetized rat stomachs.

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Effects of topical application of omeprazole on transmucosal potential difference (PD), luminal pH and histamine-stimulated acid secretion were examined in anesthetized rat stomachs, and they were compared with those of systemic administration. Omeprazole was suspended in 1% CMC with NaHCO3 (pH 9.0) or dissolved in 0.1 N HCl (pH 1.0). Both omeprazole (30 mg/kg, pH 9.0) and cimetidine (100 mg/kg), given i.d., increased the pH and inhibited acid secretion induced by histamine (8 mg/kg/hr, i.v.), while basal gastric PD was markedly elevated only by the former. Similar responses in PD, pH and acid output were obtained dose-dependently after brief exposure of the stomach (10 min) to omeprazole (0.3-30 mg/kg), even in acidic conditions, but the effects of acidified omeprazole disappeared depending upon the latency period in 0.1 N HCl; there was no effect when applied at more than 30 min after dissolution. Of interest, subsequent exposure of the stomach to a mercaptane compound (cysteine, 100 mg/kg) for 30 min significantly reversed the antisecretory effect of omeprazole (both i.d. and i.g.) but not of cimetidine. These results suggest that omeprazole has a local antisecretory action even in acidic stomachs, probably through an inhibition of the H+/K+ ATPase activity, and the increase of PD caused by omeprazole may be a characteristic phenomenon seen after the blockade of H+/K+ ATPase, but is not associated with acid inhibition itself.
公益社団法人日本薬理学会の論文

Effects of topical application of acidified omeprazole on acid secretion and transmucosal potential difference in anesthetized rat stomachs.

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