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.
Gyires
K
K
Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
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