Co-regulation of mucosal nitric oxide and prostaglandin in gastric adaptive cytoprotection

被引:23
作者
Ko, JKS [1 ]
Cho, CH [1 ]
机构
[1] Univ Hong Kong, Fac Med, Dept Pharmacol, Hong Kong, Peoples R China
关键词
nitric oxide; prostaglandins; adaptive cytoprotection; ethanol; gastric defense; mucosa;
D O I
10.1007/s000110050489
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Objective: The correlation between mucosal generation of nitric oxide (NO) and prostaglandin E-2 (PGE(2)) in gastric adaptive cytoprotection was investigated. Materials and Treatment: 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 PGE(2) and leukotriene C-4 (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 C-4 level. Indomethacin significantly inhibited mucosal PGE(2) 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 PGE(2) production. Combined L-NAME and indomethacin treatment markedly potentiated ethanol-induced mucosal damage, and completely prevented the increase in cNO or PGE(2) 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.
引用
收藏
页码:471 / 478
页数:8
相关论文
共 49 条
[1]   RELEASE OF PROTECTIVE PRODUCTS, DIFFERENT FROM PROSTAGLANDINS, BY RAT STOMACHS EXPOSED TO MILD IRRITANT [J].
BALAA, MA .
DIGESTIVE DISEASES AND SCIENCES, 1989, 34 (03) :429-435
[2]   NITRIC-OXIDE MEDIATES GLUTAMATE-LINKED ENHANCEMENT OF CGMP LEVELS IN THE CEREBELLUM [J].
BREDT, DS ;
SNYDER, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (22) :9030-9033
[3]   ENDOGENOUS PROSTAGLANDINS - ITS ROLE IN GASTRIC-MUCOSAL BLOOD-FLOW AND ETHANOL ULCERATION IN RATS [J].
CHO, CH ;
CHEN, BW ;
HUI, WM ;
LUK, CT ;
LAM, SK .
PROSTAGLANDINS, 1990, 40 (04) :397-403
[4]  
CHO CH, 1994, LIFE SCI, V55, P1521
[5]   THE INFLUENCE OF ACUTE OR CHRONIC NICOTINE TREATMENT ON ETHANOL-INDUCED GASTRIC-MUCOSAL DAMAGE IN RATS [J].
CHO, CH ;
CHEN, BW ;
HUI, WM ;
LAM, SK .
DIGESTIVE DISEASES AND SCIENCES, 1990, 35 (01) :106-112
[6]   Peptidergic and cholinergic neurons and mediators in peptone-induced gastroprotection: role of cyclooxygenase-2 [J].
Ehrlich, K ;
Plate, S ;
Stroff, T ;
Gretzer, B ;
Respondek, M ;
Peskar, BM .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 1998, 274 (05) :G955-G964
[7]  
Greenberg SS, 1997, J PHARMACOL EXP THER, V282, P1044
[8]   EVIDENCE THAT ADAPTIVE CYTOPROTECTION IN RATS IS NOT MEDIATED BY PROSTAGLANDINS [J].
HAWKEY, CJ ;
KEMP, RT ;
WALT, RP ;
BHASKAR, NK ;
DAVIES, J ;
FILIPOWICZ, B .
GASTROENTEROLOGY, 1988, 94 (04) :948-954
[9]   SENSORY NEURONS SIGNAL FOR AN INCREASE IN RAT GASTRIC-MUCOSAL BLOOD-FLOW IN THE FACE OF PENDING ACID INJURY [J].
HOLZER, P ;
LIVINGSTON, EH ;
GUTH, PH .
GASTROENTEROLOGY, 1991, 101 (02) :416-423
[10]   Regulation of nitric oxide-like activity by prostanoids in smooth muscle of the canine saphenous vein [J].
Illiano, S ;
Marsault, R ;
Descombes, JJ ;
Verbeuren, T ;
Vanhoutte, PM .
BRITISH JOURNAL OF PHARMACOLOGY, 1996, 117 (02) :360-364