Ca2+ signal is involved in endothelin-1-induced internalization of endothelin type A receptor expressed in Chinese hamster ovary cells

Abstract Endothelin type A receptor (ET A R) is internalized upon agonist stimulation; however, the mechanism thereof remains controversial. In this study, we characterized the endothelin-1 (ET-1)-induced internalization of ET A R expressed in Chinese hamster ovary cells. ET-1 elicited ET A R internalization and increase in intracellular Ca 2+ concentration. ET-1-induced ET A R internalization was completely inhibited by a reduction in intracellular and extracellular Ca 2+ levels and partially suppressed by inhibitors of protein kinase C (PKC) and extracellular signal-regulated kinases 1/2 (ERK1/2), both of which are downstream molecules in ET A R signaling. These results suggest that Ca 2+ mobilization, PKC, and ERK1/2 are involved in ET-1-induced ET A R internalization.