title: Differential effects of selective cyclooxygenase (COX)-1 and COX-2 inhibitors on anorexic response and prostaglandin generation in various tissues induced by zymosan.
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 E(2) (PGE(2)) and peritoneal prostacyclin (PGI(2)) upon zymosan injection. PGE(2) 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 PGE(2) generation upon zymosan injection does not support the role of COX-2 expressed in brain in zymosan-induced anorexic response. PGE(2) generation in liver may account for peripheral role of COX-2 in zymosan-induced anorexic response.
authors.affiliation: Department of Clinical Application, Institute of Natural Medicine, University of Toyama, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Naoi
authors.forename: Suguru
authors.initials: S
authors.lastname: Kogure
authors.forename: Masataka
authors.initials: M
authors.lastname: Saito
authors.forename: Tomohito
authors.initials: T
authors.lastname: Hamazaki
authors.forename: Shiro
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000517:prevention & control*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D002149:Energy Intake; D004926:Escherichia coli; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D000077239:Meloxicam; D051379:Mice; D008815:Mice, Inbred Strains; D008892:Milk; D011453:Prostaglandins / Q000096:biosynthesis*; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D011453:Prostaglandins; D013843:Thiazines; D013844:Thiazoles; D015054:Zymosan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000077239:Meloxicam; D007213:Indomethacin