Araki S, Kawahara Y, Kariya K, Sunako M, Fukuzaki H, Takai Y
Department of Internal Medicine (1st Division), Kobe University, School of Medicine, Japan.
Biochem Biophys Res Commun. 1989 Mar 31;159(3):1072-9. doi: 10.1016/0006-291x(89)92218-3.
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.
用内皮素或血管紧张素II孵育[3H]肌醇标记的培养兔血管平滑肌细胞（VSMC），会迅速形成肌醇一磷酸、二磷酸和三磷酸（分别为IP1、IP2和IP3）。内皮素和血管紧张素II诱导这些肌醇磷酸形成的时间进程相似。内皮素诱导的IP1、IP2和IP3形成的最大水平分别约为血管紧张素II诱导水平的50%、25%和40%。IP1形成达到半最大和最大程度所需的内皮素剂量分别约为1 nM和100 nM。蛋白激酶C激活剂12-O-十四烷酰佛波醇-13-乙酸酯（TPA）抑制内皮素诱导的IP1形成，在3 nM时可见半最大抑制程度。另一种蛋白激酶C激活剂佛波醇-12,13-二丁酸酯模拟了TPA的抑制作用，但对该酶无活性的4α-佛波醇-12,13-二癸酸酯则没有这种作用。这些结果表明，在内皮素培养的VSMC中，内皮素会导致磷脂酶C介导的磷酸肌醇水解，尽管程度比血管紧张素II小，并提示蛋白激酶C调节内皮素向磷脂酶C的信号传导机制。
