Dual action of clonidine on ethanol-induced gastric lesions: is the imidazoline-preferring receptor involved?

The imidazole alpha 2-adrenoceptor agonist, clonidine, exerts a dual action on ethanol-induced gastric lesions. At lower doses, it has a gastroprotective effect which is also seen with two other alpha 2-adrenoceptor agonists - the catecholamine, alpha-methyldopa and the guanidine, guanabenz. The gastroprotective action of the three drugs is prevented by the selective alpha 2-adrenoceptor antagonist, yohimbine, suggesting that the action is mediated by alpha 2-adrenoceptors. However, at higher doses clonidine aggravates ethanol-induced gastric lesions, an effect also seen with another imidazole, oxymetazoline. The aggravating action is not prevented by yohimbine and is not seen with alpha-methyldopa and guanabenz. This suggests that it involves a receptor/mechanism other than alpha 2- possibly an imidazoline-preferring receptor but further work, including radioligand binding studies, is needed to confirm this.