Resink T J, Scott-Burden T, Bühler F R
Department of Research, University Hospital, Basel, Switzerland.
Eur J Biochem. 1990 Apr 30;189(2):415-21. doi: 10.1111/j.1432-1033.1990.tb15504.x.
Cellular responses to the vasoconstrictor peptide, endothelin, have been investigated in quiescent cultured human vascular smooth muscle cells (hVSMC). Endothelin caused intracellular alkalinization and activation of the protein synthetic enzyme S6-kinase, but such responses were not associated with any mitogenic effects of endothelin on hVSMC. In myo-[3H]inositol-prelabelled hVSMC endothelin elicited a rapid increase in inositol bis- and tris-phosphates and concomitant hydrolysis of polyphosphoinositol lipids. In [3H]arachidonate-prelabelled hVSMC endothelin promoted production of diacylglycerol, the early kinetics of which parallelled polyphosphoinositol lipid hydrolysis. Such phospholipase C activation by endothelin was sustained in hVSMC with accumulation of inositol polyphosphates being markedly protracted and the decay of diacylglycerol slow. Endothelin promoted extracellular release of [3H]arachidonate-labelled material from hVSMC which derived via deacylation of both phosphatidylinositol and phosphatidylcholine. This process was inhibited by phospholipase A2 and lipoxygenase inhibitors, but insensitive to phospholipase C and cyclooxygenase inhibitors. Endothelin-induced activation of phospholipase C and phospholipase A2 signal transduction pathways (EC50 approximately 5-8 nM for both) in hVSMC apparently proceed in an independent parallel manner rather than a sequential one.
在静止培养的人血管平滑肌细胞（hVSMC）中，已对细胞对血管收缩肽内皮素的反应进行了研究。内皮素可引起细胞内碱化以及蛋白质合成酶S6激酶的激活，但这些反应与内皮素对hVSMC的任何促有丝分裂作用均无关。在肌醇-[3H]肌醇预标记的hVSMC中，内皮素引起肌醇二磷酸和三磷酸迅速增加，并伴随多磷酸肌醇脂质的水解。在[3H]花生四烯酸预标记的hVSMC中，内皮素促进二酰基甘油的产生，其二酰基甘油的早期动力学与多磷酸肌醇脂质水解平行。内皮素对磷脂酶C的这种激活在hVSMC中持续存在，肌醇多磷酸的积累明显延长，二酰基甘油的衰减缓慢。内皮素促进hVSMC中[3H]花生四烯酸标记物质的细胞外释放，该物质通过磷脂酰肌醇和磷脂酰胆碱的脱酰作用产生。该过程受磷脂酶A2和脂氧合酶抑制剂抑制，但对磷脂酶C和环氧化酶抑制剂不敏感。内皮素诱导的hVSMC中磷脂酶C和磷脂酶A2信号转导途径的激活（两者的EC50约为5-8 nM）显然以独立平行的方式进行，而不是顺序进行。
