Endothelin stimulates phospholipase C in cultured vascular smooth muscle cells.
Cultured vascular smooth muscle cells from bovine and rat thoracic aortae and from human omental vessels have been examined for cellular responses to endothelin. In myo-[3H]-inositol-prelabelled cells endothelin induced a rapid (within 30 sec) and protracted increase of [3H]-inositol content in inositol bis- and tris-phosphates. Concomitantly, significant polyphosphoinositide hydrolysis occurred within 30 sec. Accumulation of [3H]-inositol monophosphate and hydrolysis of phosphatidylinositol were delayed. In cells prelabelled with [3H]-arachidonic acid endothelin promoted rapid production of [3H]-diacylglycerol which decayed slowly toward control values after reaching maximum levels (1-2 min). Half-maximally effective concentrations of endothelin for all these cellular responses were comparable (approximately 3-7 nM) and not significantly different between the vascular cell isolates. The involvement of the phospholipase C-signal transduction pathway in mediating endothelin-induced vasoconstriction is invoked.
Resink
T J
TJ
Department of Research, University Hospital, Basel, Switzerland.
Scott-Burden
T
T
Bühler
F R
FR
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism; D016232:Endothelins; D004730:Endothelium, Vascular; D006801:Humans; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D010455:Peptides / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism*
D001095:Arachidonic Acids; D004075:Diglycerides; D016232:Endothelins; D007295:Inositol Phosphates; D010455:Peptides; D010716:Phosphatidylinositols; D016718:Arachidonic Acid; D007294:Inositol; D010738:Type C Phospholipases