Contribution of Prostaglandin E2 to Bradykinin-lnduced Contraction in Rabbit Urinary Detrusor

Abstract

Bradykinin (100 pM to 1 μM) contracted the rabbit urinary detrusor in vitro. The sensitivity to bradykinin was about 1000 times higher than that to acetylcholine (ACh) on a molar basis. The contractile response to bradykinin was unaffected by atropine, diphenhydramine, FPL-55712, methysergide, prazosin or tetrodotoxin, indicating that the contraction was not mediated via the release of ACh, histamine, peptide leukotrienes, serotonin or catecholamine. The bradykinin-induced contraction was, however, inhibited by indomethacin (5 μM), a cyclo-oxygenase inhibitor. Caffeic acid (10 μM), a lipoxygenase inhibitor, did not affect the contraction. Bradykinin (1 nM to 100 nM) stimulated the release of prostaglandin E2 from the detrusor in a concentration-dependent manner, and the release was abolished by treatment with indomethacin (5 μM). Prostaglandin (PG) E2 contracted the urinary detrusor with an EC50 of about 0.1 μM. Adenosine 5’-triphosphate (ATP), a stimulator of PG synthesis, also contracted the muscle with an EC50 of about 100 μM. [14C]Arachidonic acid was converted to PGE2 and F2α when it was incubated with the 700×g supernatant of the muscle homogenate. However, neither bradykinin nor ATP stimulated the PG synthesis in the supernatant. These results showed that bradykinin and ATP did not affect the cyclooxygenase and/or PG degradation system. On the other hand, when the intact detrusor muscle was incubated with [14C]arachidonic acid, bradykinin and ATP stimulated the PG synthesis, and the stimulated synthesis was inhibited by indomethacin. Mepacrine, a phospholipase A2 inhibitor, more potently inhibited the bradykinin- and ATP-induced contractions than the ACh-induced one. Therefore, bradykinin as well as ATP would stimulate phospholipase, probably the A2-type, after binding of its receptor, and contract rabbit urinary detrusor mediated via PGE2 converted from arachidonic acid.