标题:Differential Effects of Selective Cyclooxygenase (COX)-1 and COX-2 Inhibitors on Anorexic Response and Prostaglandin Generation in Various Tissues Induced by Zymosan
摘要: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.