Inhibition of canine gastric acid secretion by an H-1 receptor antagonist to histamine

Abstract

Histamine H-2 receptors are thought to mediate gastric acid secretory responses, where-as H-1 receptors supposedly regulate mucosal vascular responses to histamine. In an in vivo chambered canine stomach flap preparation, the H-1 receptor antagonist, tripelennamine, injected intraarterially (22.1 μmol/kg) into the stomach flap reduced histamine-stimulated (1.25 μ/kg/min intravenously) acid secretion by approximately two thirds with a secondary reduction in gastric mucosal blood flow. This antisecretory action does not appear to be due to nonspecific mucosal damage. The H-2 receptor antagonist, metiamide, injected intraarterially (2.5 μmol/kg) also inhibited gastric acid secretion by about two thirds as did intravenously injected metiamide (4.5 μmol/kg), whereas intravenously administered tripelennamine (40.8 μmol/kg) was ineffective as an acid secretory inhibitor. Intraarterial tripelennamine reduced the secretory actions of the H-2 agonist, 4-methyl-histamine (2.2 μg/kg/min intravenously), while intravenous metiamide depressed the gastric mucosal dilator responses to the H-1 agonist, 2-methylhistamine (5 μg/kg/min intravenously). Both histamine-receptor antagonists also reversed the systemic circulatory depressor effects of histamine and its analogs. These results suggest the need for reevaluation of inferences based upon the assumed specificity of H-2 and H-1 agonists and antagonists.