Stimulation of phospholipase C-mediated hydrolysis of phosphoinositides by endothelin in cultured rabbit aortic smooth muscle cells.
Incubation of the [3H] inositol-labeled cultured rabbit vascular smooth muscle cells (VSMCs) with either endothelin or angiotensin II caused a rapid formation of inositol mono-, bis- and trisphosphates (IP1, IP2 and IP3, respectively). Time courses of the endothelin- and angiotensin II-induced formation of these inositol phosphates were similar. The maximal levels of IP1, IP2 and IP3 formation induced by endothelin were about 50%, 25% and 40%, respectively, of those induced by angiotensin II. The doses of endothelin necessary for the half maximal and maximal extents of the formation of IP1 were about 1 nM and 100 nM, respectively. Protein kinase C-activating 12-Q-tetradecanoylphorbol-13-acetate (TPA) inhibited the endothelin-induced formation of IP1 with the half maximal extent of inhibition seen at 3 nM. The inhibitory action of TPA was mimicked by another protein kinase C-activating phorbol ester, phorbol-12,13-dibutyrate, but not by 4 alpha-phorbol-12,13-didecanoate, known to be inactive for this enzyme. These results indicate that endothelin causes the phospholipase C-mediated hydrolysis of phosphoinositides, though to a lesser extent than angiotensin II, in cultured VSMCs and suggest that protein kinase C modulates the signaling mechanism of endothelin to the phospholipase C.
Araki
S
S
Department of Internal Medicine (1st Division), Kobe University, School of Medicine, Japan.
Kawahara
Y
Y
Kariya
K
K
Sunako
M
M
Fukuzaki
H
H
Takai
Y
Y
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009529:Nicardipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D016232:Endothelins; D010455:Peptides; D010703:Phorbol Esters; D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D007294:Inositol; D009529:Nicardipine; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate