Inhibition of canine gastric acid secretion by an H-1 receptor antagonist to histamine.
Histamine H-2 receptors are thought to mediate gastric acid secretory responses, whereas 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 mumol/kg) into the stomach flap reduced histamine-stimulated (1.25 micron/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 mumol/kg) also inhibited gastric acid secretion by about two thirds as did intravenously injected metiamide (4.5 mumol/kg), whereas intravenously administered tripelennamine (40.8 mumol/kg) was ineffective as an acid secretory inhibitor. Intraarterial tripelennamine reduced the secretory actions of the H-2 agonist, 4-methylhistamine (2.2 micron/kg/min intravenously), while intravenous metiamide depressed the gastric mucosal dilator responses to the H-1 agonist, 2-methylhistamine (5 micron/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.
D000818:Animals; D004058:Diffusion; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply / Q000502:physiology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D008785:Metiamide / Q000008:administration & dosage / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014309:Tripelennamine / Q000008:administration & dosage / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D008761:Methylhistamines; D014309:Tripelennamine; D008785:Metiamide