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

Abstract Endothelintype A receptor ( ETA 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 ETA R expressedin Chinese hamster ovary cells. ET-1 elicited ETA R internalization and increase in intracellular Ca 2+ concentration. ET-1-induced ETA 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 kinases1/2 (ERK1/2), both of which are downstream molecules in ETA R signaling. These results suggest that Ca 2+ mobilization, PKC, and ERK1/2 are involved in ET-1-induced ETA R internalization.