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Abstract

Mechanisms of gastric proton pump inhibition by calcium channel antagonists.

J Nandi, R L King, D S Kaplan and R A Levine
Journal of Pharmacology and Experimental Therapeutics March 1990, 252 (3) 1102-1107;
J Nandi
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R L King
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D S Kaplan
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R A Levine
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Abstract

The inhibitory effects of Ca channel antagonists on gastric acid secretion [[14C]-aminopyrine (AP) uptake ratio] have been analyzed in isolated rabbit parletal cells (PC). Secretagogue-stimulated AP uptake was inhibited by verapamil and diltiazem in a dose-dependent manner with IC50 values of 15 and 100 microM, respectively, both in the presence and absence of extracellular Ca. In contrast, nifedipine had no effect on AP accumulation. Verapamil decreased histamine-stimulated respiration with the same IC50 as observed for AP uptake. Imidazole, a weak base, by buffering the acid spaces in PC, reversed the inhibitory effect of verapamil on respiration. In the bullfrog gastric mucosa, forskolin-stimulated proton transport was inhibited by verapamil (10(-4) M) from the luminal but not the serosal side. This inhibitory effect was reversed by either elevating KCl concentration in, or removing the drug from, the secretory solution. Verapamil inhibited gastric microsomal H+,K(+)-adenosine triphosphatase (H+,K(+)-ATPase) and PC K(+)-stimulated p-nitrophenyl phosphatase activities with a higher potency than diltiazem. Inhibition of these enzymes by verapamil and diltiazem was pH dependent. The drugs competed with K+ in both H+,K(+)-ATPase and K(+)-stimulated p-nitrophenyl phosphatase reactions. Our data suggest that inhibition of the gastric proton pump by verapamil or diltiazem is not due to their Ca channel antagonism but to their interaction with the luminal high affinity K(+)-site of the H+,K(+)-ATPase under acidic conditions.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 252, Issue 3
1 Mar 1990
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Abstract

Mechanisms of gastric proton pump inhibition by calcium channel antagonists.

J Nandi, R L King, D S Kaplan and R A Levine
Journal of Pharmacology and Experimental Therapeutics March 1, 1990, 252 (3) 1102-1107;

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Abstract

Mechanisms of gastric proton pump inhibition by calcium channel antagonists.

J Nandi, R L King, D S Kaplan and R A Levine
Journal of Pharmacology and Experimental Therapeutics March 1, 1990, 252 (3) 1102-1107;
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