Effect of acid inhibition on the growth of parietal cells.

Abstract

Studies in the rat have shown that prolonged inhibition of acid secretion by high doses of a histamine H2 antagonist is followed by a 20-30% increase in the number of parietal cells, and that this is paralleled by an augmentation of the maximum acid output. A similar effect has been shown after prolonged acid neutralization with high doses of an antacid. These trophic effects are not unexpected. An increase in gastric pH is followed by gastrin release, and the parietal cell mass may be augmented by repeated exogenous administration of gastrin or by endogenous hypergastrinaemia following surgery. To further evaluate whether a direct correlation exists between the magnitude of drug-induced hypergastrinaemia and parietal cell hyperplasia, rats were treated for 24 days with two acid inhibitors which differ markedly in the degree of acid inhibition and acute or chronic gastrin release. Six animals each were treated with either omeprazole (40 mumol/kg once daily), or atropine (3 mg/kg twice daily), or omeprazole combined with atropine or with placebo. On day 24, plasma gastrin was elevated more than 10-fold in both groups of rats treated with omeprazole but not in animals given atropine alone. As compared to placebo treatment, total parietal cell volume was significantly higher in animals treated with atropine (102 +/- 9 mm3 versus 140 +/- 18 mm3), but was unchanged in the other two groups. These studies demonstrate that marked prolonged drug-induced hypergastrinaemia does not necessarily exert trophic effects on parietal cells. Furthermore, the finding that omeprazole abolishes the effect of atropine suggests that omeprazole interferes with trophic actions on parietal cells.