Co-regulation of mucosal nitric oxide and prostaglandin in gastric adaptive cytoprotection.
OBJECTIVE
The correlation between mucosal generation of nitric oxide (NO) and prostaglandin E2 (PGE2) in gastric adaptive cytoprotection was investigated.


METHODS
Male Sprague-Dawley rats were pretreated with either N(w)-nitro-L-arginine methyl ester (L-NAME, 12.5 mg/kg i.v.) or indomethacin (5 mg/kg s.c.). Following that, mild irritant 20% ethanol was administered, 15 min prior to 100% ethanol challenge.


METHODS
Macroscopic gastric mucosal damage, NO synthase activity, mucosal PGE2 and leukotriene C4 (LTC4) levels were measured.


RESULTS
Administration of L-NAME and indomethacin significantly reduced the protective action of 20% ethanol against 100% ethanol-induced gastric mucosal damage. Besides, mucosal activity of constitutive NO (cNO) synthase, but not of the inducible isozyme (iNO synthase), was elevated following 20% ethanol treatment. This was accompanied by a reduction in mucosal leukotriene C4 level. Indomethacin significantly inhibited mucosal PGE2 biosynthesis but increased cNO synthase activity. Nevertheless, L-NAME reduced both cNO and iNO formation and prevented the increase in cNO formation caused by 20% ethanol, while enhancing mucosal PGE2 production. Combined L-NAME and indomethacin treatment markedly potentiated ethanol-induced mucosal damage, and completely prevented the increase in cNO or PGE2 biosynthesis when either compound was given alone.


CONCLUSIONS
These findings suggest a co-regulatory relationship between mucosal NO and PG in the gastric defense system, which will be released after activation by the mild irritants to induce cytoprotection.
Ko
J K
JK
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, China.
Cho
C H
CH
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005756:Gastritis / Q000517:prevention & control*; D007213:Indomethacin / Q000494:pharmacology; D017997:Leukotriene C4 / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D017997:Leukotriene C4; D009569:Nitric Oxide; D000431:Ethanol; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin