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.
Department of Pharmacology, Goa Medical College, India.
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Bhandare
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Rataboli
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D'Souza
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D006143:Guanabenz / Q000494:pharmacology; D054755:Imidazoline Receptors; D008297:Male; D008750:Methyldopa / Q000494:pharmacology; D010109:Oxymetazoline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D013270:Stomach / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D054755:Imidazoline Receptors; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D015016:Yohimbine; D000431:Ethanol; D008750:Methyldopa; D010109:Oxymetazoline; D006143:Guanabenz; D003000:Clonidine