Alpha-2 adrenergic and opioid receptor-mediated gastroprotection

Clonidine inhibited the development of gastric mucosal lesions induced by e ither acidified ethanol or indomethacin. The ED50 values were: 7.1 and 5.2 mu g.kg(-1) orally, respectively. The gastroprotective effect was antagonis ed by the pre-synaptic alpha-2 antagonist, yohimbine, the more selective al pha-2 antagonist Ch-38083 and the pre-synaptic alpha-2B antagonist prazosin . Moreover, the non-selective opioid receptor antagonist naloxone, the delt a receptor selective naltrindole also reversed the clonidine-induced mucosa l protective action. Clonidine was also effective following intracerebroven tricular administration with the ED50 of 37 ng/rat against ethanol-induced mucosal damage. Our results suggest that: 1) the gastroprotective effect of clonidine is likely to be mediated by alpha-2B adrenoceptor subtype; 2) th ere is an interaction between pre-synaptic alpha-2 adrenoceptors and opioid system; and 3) clonidine can induce gastroprotection by central mechanism. (C) 2000 Elsevier Science Ltd. Published by Editions scientifiques et medi cales Elsevier SAS.