Endothelin-3 activates a voltage-gated Ca channel via a pertussis toxin sensitive mechanism leading to dopamine release from PC12 cells.
We have investigated the role of endothelin-3 (ET-3) in the stimulus-secretion coupling mechanism in rat pheochromocytoma PC12 cells. ET-3 (10-100 nM) evoked both dopamine (DA) release and an increase in intracellular Ca2+ concentration ([Ca]i). The ET-3-evoked DA release was partially inhibited by pretreatment with pertussis toxin (PTX; 2 ng/ml, 20 h). The release was also attenuated by the voltage-gated Ca channel (VGC) blockers Cd2+ (300 microM) or nicardipine (30 microM) and was completely abolished when external Ca2+ was removed. ET-3-evoked [Ca]i increase was attenuated by the application of these VGC blockers and by pretreatment with PTX, and was abolished by removal of extracellular Ca2+. Removal of external Na+ had no effect on either response. In light of these findings, we conclude that ET-3 evokes both DA release and an increase in [Ca]i by a mechanism which involves the activation of PTX-sensitive VGCs and the resultant influx of Ca2+.
Koizumi
S
S
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Inoue
K
K
Kataoka
Y
Y
Niwa
M
M
Takanaka
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004594:Electrophysiology; D016232:Endothelins / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D016716:PC12 Cells; D037342:Pertussis Toxin; D051381:Rats; D013268:Stimulation, Chemical; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D015220:Calcium Channels; D016232:Endothelins; D010566:Virulence Factors, Bordetella; D009529:Nicardipine; D037342:Pertussis Toxin; D002118:Calcium; D004298:Dopamine