RECEPTORS FOR BRADYKININ AND PROSTAGLANDIN E-2 COUPLED TO CA2+ SIGNALING IN RAT CORTICAL COLLECTING DUCT

In freshly isolated rat cortical collecting ducts (CCD) we measured in tracellular Ca2+ activity ([Ca2+](i)) with the Fura-2 method, Bradykin in (BK) induced a transient and biphasic increase in [Ca2+](i). This i ncrease was concentration dependent and was half maximal at a concentr ation of 15 nM. The B-2 receptor antagonist HOE 140 (100 nM, n = 6) co mpletely abolished BK (100 nM) induced increase in [Ca2+](i). The B-1 receptor agonist des-Arg(9)-bradykinin (100 nM, n = 4) had no effect o n [Ca2+](i). In the absence of extracellular Ca2+, the maximal increas e in [Ca2+](i) induced by BK was diminished and the secondary plateau phase was completely abolished. Prostaglandin E-2 (PGE(2)) elevated [C a2+](i) also concentration-dependently and biphasically. A half maxima l effect was reached with 1 nM PGE(2). The secondary plateau phase was absent when extracellular Ca2+ was removed. Sulprostone (100 nM, n = 6) mimicked the PGE(2) (100 nM) induced increase in [Ca2+](i). The eff ect of BK (100 nM) on [Ca2+](i) was not inhibited by the cyclooxygenas e inhibitor indomethacin (10 mu M, n = 5). Dopamine (1 mu M, n = 4) di d not significantly alter [Ca2+](i). BK and PGE(2) regulate [Ca2+](i) in the rat CCD via release of Ca2+ from intracellular Ca2+ stores as w ell as via Ca2+ influx from extracellular space. BK directly modulates [Ca2+], through B-2 receptors. EP1 receptors are most likely to be re sponsible for the PGE(2) induced increase in [Ca2+](i).