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) exert ed gastric mucosal protective effect against acidified ethanol. Evidence wa s obtained that the gastroprotective effect of clonidine was blocked by i.c .v. injected alpha(2)-adrenoceptor antagonists yohimbine (non-subtype selec tive antagonist), prazosin and 2-[2-(4-(O-methoxyphenyl)piperazin-1-yl)ethy l]-4,4-dimethyl-1,3-(2H,4H)-isoquinolindlone (ARC-239) (representative alph a(2B/2C)-adrenoceptor blocking agents) and opioid receptor antagonists nalo xone (a non-selective, moderately mu-opioid receptor preferring antagonist) , naltrindole and naltriben delta-opioid receptor antagonists). The central ly injected naltrindole (0.5 nmol/rat) antagonised also the gastroprotectiv e 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 - recep tors are likely to be involved in the gastric mucosal protective effect of clonidine. (C) 2000 Elsevier Science B.V. All rights reserved.