PHARMACOLOGICAL EVIDENCE FOR HISTAMINE-H3 RECEPTOR IN THE CONTROL OF GASTRIC-ACID SECRETION IN CATS

We investigated the possible involvement of H-3 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 H-3 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 < 0.01) and HP (36 +/- 5%, P < 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 < 0.01) in MS and HP, respectively. These inhibitions were completely prevented by 10 nmol.kg-1.h-1 iv of the selective H-3 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 H-2 receptor antagonist ranitidine, which showed a strong inhibitory effect. These findings suggest that pentagastrin- or meal-induced gastric acid secretion involves an H-3 receptor pharmacologically distinct from the H-2 receptor.