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 acid and pepsin production has been investigated in pylorus-ligated rats.2 Intracerebroventricular injections (i.c.v.) of the selective H-3 agonist, R-alpha-methylhistamine (0.5-50 nnol per rat) caused a dose-dependent inhibition of gastric acid secretion while intravenous administration (5-500 nmol per rat) was completely ineffective.3 I.c.v. microinjections of mepyramine, tiotidine and thioperamide (51 nmol per rat), selective antagonists at H-1-, H-2- and H-3-sites respectively, failed 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 completely inactive.5 Unlike acid secretion, pepsin production was not significantly affected by all the tested compounds.6 These findings provide the first pharmacological evidence that the activation of central H3 histamine receptors exerts a negative control in the regulation of gastric acid secretion in conscious pylorus-ligated rats.