Alpha 2-adrenoceptor-mediated inhibition of gastric acid secretion by medetomidine is efficiently antagonized by atipamezole in rats.
The effect of a novel highly selective alpha 2-adrenoceptor agonist, medetomidine (4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole), was studied on gastric secretion in conscious and anaesthetized rats. Medetomidine (3-30 micrograms/kg s.c.) inhibited basal gastric acid and fluid output in conscious rats in a dose-dependent manner, while in anaesthetized rats no effect was observed when administered i.v. at the doses of 1-1000 micrograms/kg. Furthermore, medetomidine did not modify gastric acid output stimulated by infusion of histamine i.v. in anaesthetized rats, suggesting also that a medetomidine-induced change in gastric secretion does not involve any action on histamine H2-receptors. Furthermore, evidence was given indicating that alpha 2-adrenoceptors mediate the antisecretory action of medetomidine, since a low dose (0.1 mg/kg s.c., -30 min) of a selective alpha 2-adrenoceptor antagonist, atipamezole [MPV 1248, 4-(2-ethyl-2,3-dihydro-1H-inden-2-yl)-1H-imidazole] efficiently antagonized the effects of medetomidine (30 micrograms/kg s.c.) in conscious rats. In summary, medetomidine inhibits gastric secretion in the rat via alpha 2-adrenoceptor activation, the antisecretory action being blocked by atipamezole. Probably due to its high specificity for alpha 2-adrenoceptors, medetomidine did not show a stimulatory effect on gastric acid secretion in anaesthetized rats.
Savola
M
M
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Savola
J M
JM
Puurunen
J
J
D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005744:Gastric Acid / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D020926:Medetomidine; D011708:Pylorus / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014630:Vagus Nerve / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole; D006632:Histamine; D020926:Medetomidine