Effects of topical application of acidified omeprazole on acid secretion and transmucosal potential difference in anesthetized rat stomachs.
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.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Nishiwaki
H
H
Okabe
S
S
D000279:Administration, Cutaneous; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D004566:Electrodes; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014520:Urethane / Q000494:pharmacology
D006633:Histamine Antagonists; D014520:Urethane; D002927:Cimetidine; D006632:Histamine; D003545:Cysteine; D009853:Omeprazole