Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Differential Effects of Selective Cyclooxygenase (COX)-1 and COX-2 Inhibitors on Anorexic Response and Prostaglandin Generation in Various Tissues Induced by Zymosan
Kazuhisa NaoiSuguru KogureMasataka SaitoTomohito HamazakiShiro Watanabe
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2006 Volume 29 Issue 7 Pages 1319-1324

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Abstract

We have shown that anorexic response is induced by intraperitoneal injection of zymosan in mice, although the role of prostaglandins in this response is relatively unknown as compared with lipopolysaccharide (LPS)-induced anorexic response. Indomethacin (0.5 and 2.0 mg/kg), a non-selective cyclooxygenase (COX) inhibitor, as well as meloxicam (0.5 mg/kg), a selective COX-2 inhibitor, but not FR122047 (2.0 mg/kg), a selective COX-1 inhibitor, attenuated zymosan-induced anorexia. Zymosan injection elevated COX-2 expression in brain and liver but not in small intestine and colon. Meloxicam (0.5 mg/kg) and FR122047 treatment (2.0 mg/kg) similarly suppressed the generation of brain prostaglandin E2 (PGE2) and peritoneal prostacyclin (PGI2) upon zymosan injection. PGE2 generation in liver upon zymosan injection was suppressed by meloxicam (0.5 mg/kg) but not by FR122047 treatment (2.0 mg/kg). Our observations suggest that COX-2 plays an important role in zymosan-induced anorexia, which is a similar feature in LPS-induced anorexic response. However, non-selective inhibition by selective COX-1 and COX-2 inhibitors of brain PGE2 generation upon zymosan injection does not support the role of COX-2 expressed in brain in zymosan-induced anorexic response. PGE2 generation in liver may account for peripheral role of COX-2 in zymosan-induced anorexic response.

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© 2006 The Pharmaceutical Society of Japan
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