Functional role of Na+/H+ exchanger in Ca 2+ influx mediated via human endothelin type A receptor stably expressed in Chinese hamster ovary cells

Abstract

This study examines the functional role of Na+/H+ exchanger (NHE) in Ca2+ influx mediated by human endothelin type A receptor (ETAR) expressed in Chinese hamster ovary (CHO) cells. Endothelin-1 (ET-1) increased extracellular acidification rate (ECAR), which was abolished by 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an NHE inhibitor. EIPA and KB-R7943, a Na+/Ca2+ exchanger (NCX) inhibitor, inhibited ET-1-induced sustained increases in intracellular Ca2+ concentration ([Ca2+]i), and EIPA had no effect on [Ca2+]i after KB-R7943 treatment. ET-1-elicited sustained [Ca2+]i increase was suppressed by reducing extracellular Na+ concentration. These results suggest that possible coupling of NHE with NCX via Na+ transport is involved in ETAR- mediated sustained [Ca2+]i increase. ©2008 The Japanese Pharmacological Society.