AJP - Gastrointestinal and Liver Physiology, Vol 265, Issue 4 752-G758, Copyright © 1993 by American Physiological Society

ARTICLES

Role of histamine2 receptor in increased expression of rat gastric H(+)-K(+)-ATPase alpha-subunit induced by omeprazole

A. Tari, G. Yamamoto, K. Sumii, M. Sumii, Y. Takehara, K. Haruma, G. Kajiyama, V. Wu, G. Sachs and J. H. Walsh
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.

Omeprazole is a specific inhibitor in vivo of the functioning gastric acid pump, the H(+)-K(+)-adenosinetriphosphatase (ATPase), in the secretory canaliculus of the parietal cell. It has been shown previously that omeprazole in rats led to an increase in the mRNA for the alpha-subunit of the H(+)-K(+)-ATPase. Omeprazole causes a marked increase in circulating gastrin in this species, which in turn stimulates release of histamine from the enterochromaffin-like cell. The possible role of this pathway was investigated by the in vivo administration of famotidine, a potent H2 receptor antagonist. A single intraperitoneal dose of famotidine, 200 mg/kg, produced a transient hypergastrinemia peaking at 3 h and normalizing at 12 h, inhibition of secretion that lasted for 12 h, but no change in the level of the alpha-subunit mRNA or of beta-actin mRNA. In contrast, a single dose of omeprazole, 100 mg/kg, inhibited acid secretion and produced hypergastrinemia, peaking at 12 h, both effects lasting for the 24-h observation period. Omeprazole elevated the alpha-subunit mRNA transiently by more than threefold at 3 h, with normal levels being restored at 24 h. The administration of famotidine 1 h after omeprazole did not change the effects of omeprazole on acid secretion but elevated the gastrin levels further. There was now no elevation of the alpha-subunit mRNA for the first 6 h, but a small increase at 12 h and a further increase to approximately 2.5-fold at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				J. Del Valle and I. Gantz Novel insights into histamine H2 receptor biology Am J Physiol Gastrointest Liver Physiol, November 1, 1997; 273(5): G987 - G996. [Abstract] [Full Text] [PDF]