Activation of central opioid receptors may induce gastric mucosal defence in the rat.
The effect of different opioid peptides on acidified ethanol- and indomethacin-induced gastric mucosal lesions was studied following intracerebroventricular (i.c.v.) administration. It was found that both the selective delta opioid receptor agonists--deltorphin II, [D-Ala(2), D-Leu(5)]-enkephalin (DADLE), [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE)-, mu-opioid receptor agonist--[D-Ala(2), Phe(4), GlyT-ol]-enkephalin (DAGO)--as well as beta-endorphin inhibited the mucosal damage induced by both ethanol and indomethacin in pmolar 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 induced by DAGO in the dose of 1.9 nmol/rat. The protective effect was abolished in both ulcer models by bilateral cervical vagotomy. N(G)-nitro-L-arginine, an inhibitor of NO synthase, reduced the protective action in ethanol-induced, but not in indomethacin-induced gastric damage. The results suggest that activation of supraspinal delta and mu-opioid receptors resulted in 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 different in ethanol- and indomethacin-ulcer models: prostaglandins and nitric oxide are likely to be involved in the protective action of opioid peptides in ethanol-, but not in the indomethacin-ulcer model.
Gyires
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K
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Faculty of Medicine, 1089 Budapest, Nagyvárad tér. 4, Hungary. gyirkla@net.sote.hu
Müllner
K
K
Rónai
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AZ
D000818:Animals; D001921:Brain / Q000502:physiology*; D019610:Cytoprotection / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009294:Narcotics / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D014628:Vagotomy; D001615:beta-Endorphin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009294:Narcotics; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019335:Nitroarginine; D000431:Ethanol; D001615:beta-Endorphin; D016308:Enkephalin, Leucine-2-Alanine; D020881:Enkephalin, D-Penicillamine (2,5)-; D007213:Indomethacin