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This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.061283v1 309/3/995    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Uno, K. Articles by Yoshimura, T. Search for Related Content PubMed PubMed Citation Articles by Uno, K. Articles by Yoshimura, T. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB NITRIC OXIDE

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

In Vivo Study on Cross Talk between Inducible Nitric-Oxide Synthase and Cyclooxygenase in Rat Gastric Mucosa: Effect of Cyclooxygenase Activity on Nitric Oxide Production

Laboratory of Applied Biomedicinal Chemistry, Institute for Life Support Technology, Yamagata Public Corporation for the Development of Industry, Yamagata, Japan (K.U., T.Y.); Gastroenterology, Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan (K.U., H.S., K.I., K.K., T.S.); and Department of Biochemistry, Yamagata University School of Medicine, Yamagata, Japan (Y.I., J.F.)

The integrity of gastric mucosa during endotoxemia is maintained by the balance of inflammatory mediators, such as prostanoids originated from cyclooxygenase-2 (COX-2) and nitric oxide (NO) from inducible nitric-oxide synthase (iNOS). Thus, we elucidated in vivo cross talk between prostanoids and NO in gastric mucosa during endotoxemia, using an iNOS-specific inhibitor, N-(3-(aminomethyl)benzyl)acetamidine (1400W); a nonspecific COX inhibitor, indomethacin; and a COX-2-specific inhibitor, N-(2-[cyclohexyloxy]-4-nitrophenyl)methanesulfonamide (NS-398). Gastric mucosal NO and prostaglandin E2 (PGE2), a predominant product of COX, expressed as mean ± S.D. of five rats per group, were assayed by electron paramagnetic resonance spectrometry and enzyme immunoassay technique, respectively. The levels of NO and PGE2 increased gradually up to 6 h after administration of bacterial lipopolysaccharide (LPS) (NO: control, 0.35 ± 0.16; 6 h, 13.3 ± 3.3 nmol/g tissue/30 min; and PGE2: control, 288 ± 16; 6 h, 806 ± 15 pg/g tissue). Pretreatment with 1400W decreased the increase in NO level without any effect on the PGE2 level (NO, 4.0 ± 0.4 nmol/g tissue/30 min; PGE2, 788 ± 26 pg/g tissue). In contrast, treatment with indomethacin and NS-398 inhibited not only PGE2 level but also NO level in a dose-dependent manner without any significant effect on both iNOS and COX protein and mRNA expression. These results demonstrate that in the LPS-treated rat gastric mucosa, PGE2 enhances the release of NO after activation of iNOS, although NO produced by iNOS does not stimulate the release of PGE2 by COXs. The effect of COX activity on iNOS-NO pathway can be important in the regulation of gastric mucosal integrity in inflammatory states.

Address correspondence to: Dr. Tetsuhiko Yoshimura, Laboratory of Applied Biomedicinal Chemistry, Institute for Life Support Technology, Yamagata Public Corporation for the Development of Industry, Yamagata 990-2473, Japan. E-mail: yoshi{at}yat.ymgt-techno.or.jp

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