Endothelin-1 and endothelin-3 stimulate calcium mobilization by different mechanisms in vascular smooth muscle.
The mechanisms by which endothelin-1 (ET-1) and endothelin-3 (ET-3) stimulate Ca2+ mobilization were investigated in rat aortic smooth muscle cells. Both ET-1 and ET-3 potently stimulated mobilization of Ca2+ from intracellular stores, however only ET-1-stimulated Ca2+ mobilization appeared to occur as a consequence of an elevation in cellular inositol trisphosphate (IP3) concentration. Neomycin, an inhibitor of phospholipase C, inhibited both the increase in [3H]IP3 formation and the mobilization of Ca2+ induced by ET-1, however it did not affect Ca2+ mobilization induced by ET-3. Together these findings indicate that ET-1 stimulates Ca2+ mobilization via an increase in IP3, whereas the effect of ET-3 appears to be mediated by a separate, IP3-independent signalling pathway.
Little
P J
PJ
Baker Medical Research Institute, Prahran, Victoria, Australia.
Neylon
C B
CB
Tkachuk
V A
VA
Bobik
A
A
D000818:Animals; D001011:Aorta / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction
D016232:Endothelins; D015544:Inositol 1,4,5-Trisphosphate; D009355:Neomycin; D002118:Calcium