Receptors for bradykinin and prostaglandin E coupled to Ca 2+ signalling in rat cortical collecting duct

Abstract

In freshly isolated rat cortical collecting ducts (CCD) we measured intracellular Ca 2+ activity ([Ca 2+] i) with the Fura-2 method. Bradykinin (BK) induced a transient and biphasic increase in ([Ca 2+] i). This increase was concentration dependent and was half maximal at a concentration of 15 nM. The B 2 receptor antagonist HOE 140 (100 nM, n = 6) completely abolished BK (100 nM) induced increase in ([Ca 2+] i). The B, receptor agonist des-Arg 9-bradykinin (100 nM, n = 4) had no effect on ([Ca 2+] i). In the absence of extracellular Ca 2+, the maximal increase in [Ca 2+] i induced by BK was diminished and the secondary plateau phase was completely abolished. Prostaglandin E 2 (PGE 2) elevated ([Ca 2+] i) also concentration-dependently and biphasically. A half maximal effect was reached with 1 nM PGE 2. The secondary plateau phase was absent when extracellular Ca 2+ was removed. Sulprostone (100 nM, n = 6) mimicked the PGE 2 (100 nM) induced increase in ([Ca 2+] i). The effect of BK (100 nM) on [Ca 2+] i was not inhibited by the cyclooxygenase inhibitor indomethacin (10 μM, n = 5). Dopamine (1 μM, n = 4) did not significantly alter ([Ca 2+] i). BK and PGE 2 regulate [Ca 2+] i in the rat CCD via release of Ca 2+ from intracellular Ca 2+ stores as well as via Ca 2+ influx from extracellular space. BK directly modulates [Ca 2+] i through B 2 receptors. EP 1 receptors are most likely to be responsible for the PGE 2 induced increase in [Ca 2+] i.