Famotidine, a histamine-2-receptor antagonist, inhibits the increase in rat gastric H+/K(+)-ATPase mRNA 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 (H2)-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 H2 receptor on the parietal cell.