FAMOTIDINE, A HISTAMINE-2-RECEPTOR ANTAGONIST, INHIBITS THE INCREASE IN RAT GASTRIC H+/K+-ATPASE MESSENGER-RNA INDUCED BY INTRAVENOUS-INFUSION OF GASTRIN-17 AND HISTAMINE

We examined the effects of gastrin and histamine on rat gastric H+/K+-ATPase, the enzyme responsible for H+ secretion, gene expression in vivo. Gastrin 17 (G 17) or histamine dihydrochloride (histamine) was continuously infused through the femoral vein of anesthetized rats. Gastric H+/K+-ATPase mRNA levels were measured using northern blot analysis. Infusion of G 17 and histamine increased the H+/K+-ATPase mRNA level significantly compared with basal control level or vehicle control level (P < 0.01). However, pretreatment with famotidine, a potent histamine-2 (H-2)-receptor antagonist, inhibited the increase of rat gastric H+/K+-ATPase mRNA following G 17 and histamine infusion. These findings indicate that both histamine and G 17 increase expression of H+/K+-ATPase mRNA by activating H-2 receptor on the parietal cell.