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

• 影响指数: 3.578
• 发表时间: May 2019
• 来源期刊: J Pharmacol Sci
• DOI: 10.1016/j.jphs.2019.03.008
• PMID: 31103330
• 文章类型: Journal Article
• 中科院分区: Q3
• 方向: 医学
• 作者列表: Horinouchi T,Karki S,Terada K,Mazaki Y,Miwa S

关键词: Ca(2+) signal; Endothelin type A receptor; Internalization

Mesh: Animals; CHO Cells; Calcium / metabolism; Calcium Signaling / physiology; Cricetinae; Cricetulus; Endothelin-1 / pharmacology; Female; Mitogen-Activated Protein Kinase 3 / metabolism physiology; Protein Kinase C / metabolism physiology; Receptor, Endothelin A / metabolism; Signal Transduction / drug effects

Abstract

Endothelin type A receptor (ETAR) is internalized upon agonist stimulation; however, the mechanism thereof remains controversial. In this study, we characterized the endothelin-1 (ET-1)-induced internalization of ETAR expressed in Chinese hamster ovary cells. ET-1 elicited ETAR internalization and increase in intracellular Ca2+ concentration. ET-1-induced ETAR internalization was completely inhibited by a reduction in intracellular and extracellular Ca2+ 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 ETAR signaling. These results suggest that Ca2+ mobilization, PKC, and ERK1/2 are involved in ET-1-induced ETAR internalization.