R-ALPHA-METHYLHISTAMINE-INDUCED INHIBITION OF GASTRIC-ACID SECRETION IN PYLORUS-LIGATED RATS VIA CENTRAL HISTAMINE H-3 RECEPTORS

1 The effect of central H-3 histamine receptor activation on gastric a cid and pepsin production has been investigated in pylorus-ligated rat s. 2 Intracerebroventricular injections (i.c.v.) of the selective H-3 agonist, R-alpha-methylhistamine (0.5-50 nnol per rat) caused a dose-d ependent inhibition of gastric acid secretion while intravenous admini stration (5-500 nmol per rat) was completely ineffective. 3 I.c.v. mic roinjections of mepyramine, tiotidine and thioperamide (51 nmol per ra t), selective antagonists at H-1-, H-2- and H-3-sites respectively, fa iled to modify the acid secretory response to pylorus ligation. 4 The antisecretory effect of R-alpha-methylhistamine (5 nmol per rat, i.c.v .) was selectively prevented by the H-3-blocker, thioperamide (51 nmol per rat, i.c.v.), mepyramine and tiotidine pretreatment being complet ely inactive. 5 Unlike acid secretion, pepsin production was not signi ficantly affected by all the tested compounds. 6 These findings provid e the first pharmacological evidence that the activation of central H3 histamine receptors exerts a negative control in the regulation of ga stric acid secretion in conscious pylorus-ligated rats.