Analysis of the Inhibiting Activity of Presynaptic α2-Adrenoceptors against NSAID-induced Gastric Mucosal Lesions in the Rat

Abstract

Clonidine at a dose of 0.00625-0.025 mg/kg (po) inhibited the gastric mucosal lesions induced by indomethacin, acidified aspirin, naproxen and piroxicam. The gastroprotective effect was reversed by the α2-adrenoceptor antagonist yohimbine (5 mg/kg sc) and by the highly selective α2-adrenoceptor antagonist berbane derivative, Ch-38083 (3.5 mg/kg sc). Clonidine also decreased the gastric acid secretion in pylorus-ligated rats at a dose of 0.2 mg/kg (given intraduodenally) but not at gastroprotective doses (0.00625-0.025 mg/kg). The antisecretory effect of clonidine was reversed by both yohimbine and Ch-38083. The α2B-receptor antagonist prazosin (0.1 mg/kg sc) blocked the gastroprotective effect but failed to influence the antisecretory action of clonidine. Our data suggest that the α2B-adrenoceptor subtype might be involved in gastroprotection; however, the antisecretory effect is likely to be mediated by α2A-like adrenoceptor subtype.