Effect of intraventricular histamine on hormone secretion in dogs

In pentobarbital-anesthetized dogs, infusion of a low dose of histamine directly into the third ventricle increased plasma ACTH concentration. The increase was unaffected by metiamide, a drug which blocks H2 receptors, but was abolished by mepyramine, a drug which blocks H1 receptors. Mepyramine alone did not produce a decrease in plasma ACTH concentration in stressed dogs. Infusion of the H1 agonist 2-methylhistamine increased plasma ACTH concentration, whereas infusion of the H2 agonist 4-methylhistamine decreased plasma ACTH concentration and blocked the response to surgical stress. Histamine, 2-methylhistamine and 4-methylhistamine had no statistically significant effect on plasma renin activity, blood pressure, or heart rate, and histamine had no effect on plasma prolactin concentration. There were no consistent, specific effects on growth hormone secretion. We conclude that activation of central H1 receptors increases ACTH secretion in dogs, and that activation of central H2 receptors decreases ACTH secretion. Some of the reported effects of cyproheptadine and other drugs on ACTH secretion may be due to their antihistamine activity.