Functional evidence that gastroprotection can be induced by activation of central alpha(2B)-adrenoceptor subtypes in the rat.
Clonidine injected intracerebroventricularly (i.c.v.) (0.47 nmol/rat) exerted gastric mucosal protective effect against acidified ethanol. Evidence was obtained that the gastroprotective effect of clonidine was blocked by i.c.v. injected alpha(2)-adrenoceptor antagonists yohimbine (non-subtype selective antagonist), prazosin and 2-[2-(4-(O-methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2 H, 4H)-isoquinolindione (ARC-239) (representative alpha(2B/2C)-adrenoceptor blocking agents) and opioid receptor antagonists naloxone (a non-selective, moderately mu-opioid receptor preferring antagonist), naltrindole and naltriben delta-opioid receptor antagonists). The centrally injected naltrindole (0.5 nmol/rat) antagonised also the gastroprotective effect of clonidine --but not that of the delta-agonist [D-Ala(2), D-Leu(5)]enkephalin--administered peripherally. The results suggest that central alpha(2B/2C)-adrenoceptor subtypes and opioid--particularly delta--receptors are likely to be involved in the gastric mucosal protective effect of clonidine.
Gyires
K
K
Department of Pharmacology and Pharmacotherapy, Semmelweis University of Medicine, Nagyvárad tér 4, 1089, Budapest, Hungary.
Müllner
K
K
Rónai
A Z
AZ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology*; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D009270:Naloxone; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; C055382:naltrindole; D003000:Clonidine