Endothelin Type B Receptor–Induced Sustained Ca2+ Influx Involves Gq/11/Phospholipase C–Independent, p38 Mitogen-Activated Protein Kinase–Dependent Activation of Na+/H+ Exchanger

Abstract

The mechanism for sustained Ca2+ influx activated by G protein–coupled receptors was examined. In Chinese hamster ovary cells expressing recombinant human endothelin type B receptor (ETBR) and endogenous P2Y receptor (P2Y-R), endothelin-1 elicited a sustained Ca2+ influx depending on Gq/11 protein, phospholipase C (PLC), Na+/H+ exchanger (NHE), and p38 mitogen-activated protein kinase (p38MAPK), whereas P2Y-R–induced sustained Ca2+ influx was negligible. Functional studies showed that NHE activation by ETBR was mediated via p38MAPK but not Gq/11/PLC, while that by P2Y-R involves only Gq/11/PLC/p38MAPK. These results suggest that Gq/11/PLC-independent NHE activation via p38MAPK plays an important role in ETBR-mediated sustained Ca2+ influx. Keywords:: endothelin type B receptor, Na+/H+ exchanger, p38 mitogen-activated protein kinase