Activation of central opioid receptors may induce gastric mucosal defence in the rat

The effect of different opioid peptides on acidified ethanol- and indometha cin-induced gastric mucosal lesions was studied following intracerebroventr icular (i.c.v.) administration. It was found that both the selective delta opioid receptor agonists-deltorphin II, [D-Ala(2), D-Leu(5)]-enkephalin (DA DLE), [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE)-, mu -opioid receptor agonist - [D-Ala(2), Phe(4), GlyT-ol]-enkephalin (DAGO) - as well as P-endorphin i nhibited the mucosal damage induced by both ethanol and indomethacin in pmo lar dose range. In contrast, the gastric acid secretion was not influenced by DADLE in the dose of 16 nmol/rat and only a slight reduction (40%) was i nduced by DAGO in the dose of 1.9 nmol/rat. The protective effect was aboli shed in both ulcer models by bilateral cervical vagotomy. N-G-nitro-L-argin ine, an inhibitor of NO synthase, reduced the protective action in ethanol- induced, but not in indomethacin-induced gastric damage. The results sugge st that activation of supraspinal delta and mu -opioid receptors resulted i n inhibition of gastric mucosal lesions elicited by ethanol or indomethacin . The gastroprotective action is independent from the effect of opioids on acid secretion. Vagal nerve is involved in conveying the central action to the periphery. The mechanism of the gastroprotective effect of opioids is d ifferent in ethanol- and indomethacin- ulcer models: Prostaglandins and nit ric oxide are likely to be involved in the protective action of opioid pept ides in ethanol-, but not in the indomethacin- ulcer model. (C) 2001 Publis hed by Elsevier Science Ltd.