Possible mechanism of endothelin-induced Ca2+ mobility in A7r5 cultured vascular smooth muscle cells.
We studied the mechanism by which endothelin-1 (ET-1) affects the mobility of intracellular free Ca2+ ([Ca2+]i) in cultured A7r5 aortic smooth muscle cells. ET-1 at 10(-9) to 10(-7) M increased [Ca2+]i in Ca2+-containing buffer and Ca2+-free buffer. Pretreatment with ET-1 inhibited thapsigargin- and carbonylcyanide m-chlorophenylhydrazone (CCCP)-induced [Ca2+]i increases in Ca2+-free buffer. Pretreatment with thapsigargin and CCCP partially abolished the [Ca2+]i increase induced by ET-1. The ET-1-induced Ca2+ signal was partially suppressed by the ETA receptor antagonist BQ123 and the ETB receptor antagonist BQ788 and nifedipine. Pretreatment of cells with the phospholipase C inhibitor U73122 reduced the ET-1-induced [Ca2+]i increase. These results suggest that the ET-1-induced [Ca2+]i increase in A7r5 smooth muscle cells initially activates the ETA receptor, leading to Ca2+ influx and increased internal Ca2+ release from endoplasmic reticulum and mitochondrial Ca2+ stores. The ETB receptor and L-type Ca2+ channel are involved in maintaining further extracellular Ca2+ influx. ET-1-induced intracellular Ca2+ release was also modulated by phospholipase C-coupled events.
Hong
Show-Jen
SJ
Department of Pharmacology, Kaohsiung Medical University, Kaohsiung, Taiwan. hong6657@ms5.hinet.net
Fong
Jim C
JC
Hwang
Jia-Huae
JH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology
D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; C086539:BQ 788; D010738:Type C Phospholipases; D009543:Nifedipine; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium