Intrinsic prostacyclin contributes to exudation induced by bradykinin or carrageenin: A study on the paw edema induced in IP-receptor-deficient mice

To prove that prostaglandin I-2 (PGI(2)) is a major prostaglandin involved in bradykinin-induced exudation, we examined carrageenin- or bradykinin-ind uced paw edema in prostacyclin receptor-deficient mice (IPKO). Paw volume o f wild-type mice (IPWT) increased gradually 5-6 hr after the carrageenin in jection in a similar manner as in ICR mice, but the swelling in IPKO mice w as significantly smaller (about 60% of the IPWT volume). Indomethacin, at 1 0 mg/kg, suppressed the swelling of the IPWT paw to the level of the non-pr etreated IPKO, which was not affected by indomethacin, confirming the previ ous result that PGI(2) is a major prostaglandin involved in the swelling. T he paw edema of IPWT and IPKO was significantly; attenuated by the nonpepti de bradykinin B2-receptor antagonist FR173657, at 30 mg/kg, to the same lev el of swelling, indicating kinin involvement. Injection of bradykinin (1.2 nmole) into the paw caused rapid edema, which peaked around 15 min in both mice. However, the edema induced in IPKO was smaller and almost at the same level as that elicited in the indomethacin-treated IPWT, suggesting that e dema induced by bradykinin includes the intrinsic effect of PGI(2). Concomi tant injection of carbacyclin with bradykinin caused enhancement of edema i n IPWT mice but not in IPKO mice, indicating that intrinsic PGI(2) could ca use enhancement of bradykinin- or even carrageenin-induced edema formation. These results clearly demonstrate that bradykinin released by carrageenin may be a key mediator to induce PGI(2) formation, and both autacoids work t ogether to induce enhanced inflammatory exudation. (C) 2000 Elsevier Scienc e Inc.