The role of endogenous nitric oxide in the gastroprotective action of morphine.
Morphine in a dose of 1 mg/kg s.c. decreased mucosal lesions induced by 100% ethanol or acidified aspirin by 79% and 85%, respectively, in rats. When the animals were pretreated with NG-nitro-L-arginine (40 mg/kg i.v.), the mucosal lesions were aggravated in both tests and the gastroprotective action of morphine decreased to 17% and 20%, respectively. This decrease in morphine protection was antagonized by L-arginine but not by D-arginine in the case of ethanol-induced lesions; however, L-arginine failed to restore the gastroprotective effect of morphine when the mucosal damage was induced by acidified aspirin. The protective action of either prostaglandin E2 (0.1 mg/kg orally) or cysteamine (50 mg/kg orally) was not influenced by NG-nitro-L-arginine (L-NNA). When L-NNA was given simultaneously with either indomethacin (10 mg/kg p.o.) or N-ethyl-maleimide (50 mg/kg s.c.), compounds which also reduced the gastroprotective action of morphine, almost complete inhibition of the gastroprotective action of morphine against 100% ethanol-induced lesions was observed as a result of the addition of the inhibitory activities of the latter substances. These results suggest that: (1) Endogenous nitric oxide is likely to be involved in the gastroprotective action of morphine. (2) The protective action of nitric oxide is independent of both mucosal prostaglandins and sulfhydryls.
Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
K
K
Gyires
D000818:Animals; D000897:Anti-Ulcer Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001241:Aspirin; D003543:Cysteamine / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D000431:Ethanol; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019335:Nitroarginine; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control
D000897:Anti-Ulcer Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D000431:Ethanol; D003543:Cysteamine; D009020:Morphine; D001120:Arginine; D015232:Dinoprostone; D005033:Ethylmaleimide; D001241:Aspirin