Activation of phospholipase A2 by endothelin in cultured vascular smooth muscle cells.
The ability of endothelin to promote phospholipid hydrolysis has been studied in myo-[2-3H]-inositol-, [3H]-arachidonic acid- or methyl-[3H]choline chloride-prelabelled cultured vascular smooth muscle cells (VSMC) from rat and bovine thoracic aortae and human omental vessels. The biochemical responses to endothelin were comparable between the different VSMC isolates. Endothelin promoted the accumulation of glycerolphospho[3H]inositol and concomitant loss of [3H]-inositol label from phosphatidylinositol. Exposure of [3H]choline-labelled VSMC to endothelin resulted in a loss of radioactivity from phosphatidylcholine that was inversely parallelled by an increase in water-soluble [3H]-choline metabolites. In [3H]-arachidonic acid ([3H]-AA)-labelled VSMC, endothelin induced extracellular release of [3H]-AA which derived from both phosphatidylcholine and phosphatidylinositol. Half-maximally effective concentrations of endothelin for all these responses were approximately 2-7 nM and did not vary between VSMC types. Endothelin-induced release of [3H]-AA into VSMC medium-overlay was inhibited by quinacrine and nordihydroguaiaretic acid but not by neomycin or indomethacin. The data herein implicate activation of phospholipase A2 by endothelin with subsequent metabolism of arachidonic acid via the lipoxygenase pathway.
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 / Q000032:analysis; D002417:Cattle; D002478:Cells, Cultured; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D007294:Inositol / Q000378:metabolism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D010455:Peptides / Q000494:pharmacology*; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D051381:Rats
D001095:Arachidonic Acids; D016232:Endothelins; D010455:Peptides; D010743:Phospholipids; D016718:Arachidonic Acid; D007294:Inositol; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2