Intracerebroventricular injection of clonidine releases beta-endorphin to induce mucosal protection in the rat

The possibility that the endogenous opioid system could be involved in the central nervous system (CNS)-mediated gastroprotective effect of clonidine was investigated. Intracerebroventricularly (i.c.v.) injected clonidine (47 0 pmol/rat) inhibited the gastric mucosal lesions induced by (orally admini stered) acidified ethanol in a significant manner in the rat. The gastropro tective effect of the centrally administered clonidine was antagonised by i .c.v, or intracisternally (i.c.) administered presynaptic alpha-2 adrenocep tor antagonist, yohimbine; the non-selective opioid receptor antagonist, na loxone; and the delta opioid receptor antagonist naltrindole. These results suggest that an interaction between central alpha-2 adrenoceptors and endo genous opioid systems is involved in mediating the mucosal protective effec t. beta-endorphin antiserum (i.c.) also antagonised the gastroprotection in duced by intracerebroventricularly injected clonidine indicating that beta- endorphin release is likely to be a key factor in the gastroprotective effe ct of clonidine. Furthermore, the i.c.v. or i.c. injection of beta-endorphi n produced a potent gastroprotection in the picomolar range. The mucosal pr otective effect of clonidine was abolished after vagotomy indicating that t he central effect may be conveyed to the periphery by vagal efferents. Sinc e atropine (1 mg/kg i.v.) failed to modify, but hexamethonium (10 mg/kg i.v .) antagonised the gastroprotective effect of clonidine, it would appear th at in the periphery nicotinic, but not muscarinic, cholinergic receptors ar e likely to be involved in the mucosal protective effect of clonidine. In c onclusion, clonidine (i.c.v.) induces gastroprotective action by releasing an endogenous opioid substance - most likely beta-endorphin - in the rat. T he clonidine-induced central gastroprotection requires the integrity of vag al pathway; cholinergic nicotinic - but not muscarinic - receptors might me diate the effect in the periphery. (C) 2000 Elsevier Science Ltd. All right s reserved.