EFFECT OF HISTAMINE ON RAT GASTRIC H-K+-ATPASE ALPHA-SUBUNIT EXPRESSION()

Effect of histamine on rat gastric H+-K+-ATPase alpha-subunit expressi on. Am. J. Physiol. 266 (Gastrointest. Liver Physiol. 29): G444-G450, 1994. - The H+-K+-adenosinetriphosphatase (ATPase) is expressed in the parietal cell and is responsible for acid secretion by the stomach. H istamine binds to an H-2 receptor and activates adenylate cyclase and intracellular calcium concentration ([Ca2+](i)) elevation, stimulating acid secretion. It has been shown that omeprazole administered to rat s increases serum gastrin and transiently increases the level of mRNA for the alpha-subunit of the pump, but this increase is blocked by the presence of the H-2-receptor antagonist, famotidine [A. Tari, G. Yama moto, K. Sumii, M. Sumii, Y. Takehara, K. Haruma, G. Kajiyama, V. Wu, G. Sachs, and J.H. Walsh. Am. J. Physiol. 265 (Gastrointest. Liver Phy siol. 28): G752-G758, 1993]. These observations suggest that the relea se of histamine induced by gastrin is essential for the increase of th e expression of mRNA induced by omeprazole. Infusion of histamine at 1 5 mu mol.kg(-1).h(-1) iv for 1 h increased the alpha-subunit mRNA leve l by 144 +/- 2.4% and induced a stimulated morphological appearance of the parietal cell. These changes were inhibited completely by the com petitive H-2-receptor antagonist famotidine, which elevated gastric pH and serum gastrin. Famotidine also reduced the level of H+-K+-ATPase mRNA compared with control animals. No change in the expression of bet a-actin mRNA was observed in any group of animals. These data provide direct evidence for histamine stimulation of H+-K+-ATPase alpha-subuni t gene expression by activation of the H-2 receptor.