PT  - JOURNAL ARTICLE
AU  - Koh-ichi Yuhki
AU  - Akinori Ueno
AU  - Hiroaki Naraba
AU  - Fumiaki Kojima
AU  - Fumitaka Ushikubi
AU  - Shuh Narumiya
AU  - Sachiko Oh-ishi
TI  - Prostaglandin Receptors EP2, EP3, and IP Mediate Exudate Formation in Carrageenin-Induced Mouse Pleurisy
AID  - 10.1124/jpet.104.071548
DP  - 2004 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1218--1224
VI  - 311
IP  - 3
4099  - http://jpet.aspetjournals.org/content/311/3/1218.short
4100  - http://jpet.aspetjournals.org/content/311/3/1218.full
SO  - J Pharmacol Exp Ther2004 Dec 01; 311
AB  - The roles of prostaglandins (PGs) as mediators of inflammation have been extensively studied, and production of PGI2 and PGE2 at inflammatory sites has been reported. However, it has not yet been clarified which type of PG receptors has a major role in inflammatory exudation. To examine in vivo role of PG receptors in inflammatory exudation, we induced pleurisy in PG receptors (IP, EP1, EP2, EP3, or EP4) knockout mice by intrapleural injection of carrageenin. Pleural exudate accumulation in wild-type (WT) mice at 1 to 5 h, but not at 24 h, was significantly attenuated by the pretreatment with indomethacin, indicating that PGs are responsible for exudate formation at the early phase of pleurisy. Pleural exudation at 1 to 5 h in IP, EP2, or EP3 knockout mice, but not in EP1 and EP4 knockout, was significantly reduced compared with in WT mice. In the exudates, 6-keto-PGF1α and PGE2 were detected as the major PGs, each with its peak concentration at 3 h. In addition, involvement of bradykinin in the phenomenon was suggested by the fact that captopril, a kininase inhibitor, enhanced the exudate formation and increased the amount of 6-keto-PGF1α and PGE2 and that a bradykinin B2-receptor antagonist inhibited the exudate formation. In contrast, leukocyte migration into pleural cavity was not influenced by indomethacin-treatment nor by these receptor deficiencies. These results demonstrate participation of EP2 and EP3 along with IP in pleural exudate formation but not in leukocyte migration in carrageenin-induced mouse pleurisy. The American Society for Pharmacology and Experimental Therapeutics