Pharmacological evidence for histamine H3 receptor in the control of gastric acid secretion in cats.

We investigated the possible involvement of H3 receptor in the control of gastric acid secretion in the conscious cat provided with a gastric fistula [main stomach (MS)] and a denervated Heidenhain pouch (HP). Intravenous infusion of the selective H3 agonist (R)-alpha-methylhistamine at 3, 10, and 30 nmol.kg-1.h-1 induced a dose-related inhibition of pentagastrin-stimulated gastric acid output. Maximal inhibition in MS (48 +/- 3%, P less than 0.01) and HP (36 +/- 5%, P less than 0.01) was obtained with 30 nmol.kg-1.h-1. This dose also significantly inhibited peptone meal-induced gastric acid output by 38 +/- 4 and 46 +/- 8% (P less than 0.01) in MS and HP, respectively. These inhibitions were completely prevented by 10 nmol.kg-1.h-1 iv of the selective H3 receptor antagonist thioperamide. On the other hand, (R)-alpha-methylhistamine was without any effect on histamine-stimulated gastric acid output, whereas thioperamide produced a slight but not significant increase of this output in contrast to the H2 receptor antagonist ranitidine, which showed a strong inhibitory effect. These findings suggest that pentagastrin- or meal-induced gastric acid secretion involves an H3 receptor pharmacologically distinct from the H2 receptor.