Osugi T, Imaizumi T, Mizushima A, Uchida S, Yoshida H
J Pharmacol Exp Ther. 1987 Feb;240(2):617-22.
In neuroblastoma x glioma hybrid NG108-15 cells, bradykinin (BK) receptor stimulation leads to phosphoinositide hydrolysis, formation of inositol phosphates and mobilization of intracellular calcium. Treatment of the cells with 12-O-tetradecanoyl phorbol 13-acetate (TPA) suppressed the spike phase of increases in intracellular calcium concentration. In radioligand binding studies, TPA treatment did not interfere with [3H]BK specific binding to intact cells or to cell membranes. The ability of guanyl-5'-yl-imidodiphosphate to promote the conversion of the high affinity sites of the BK receptors into a low affinity sites was unaffected by TPA. TPA treatment showed the dose-dependent, noncompetitive inhibition of BK-stimulated formation of inositol trisphosphate. In the membrane preparations from TPA-treated cells, guanosine 5'-(3-O-thio)triphosphate-stimulated inositol trisphosphate formation was inhibited by 50%. These data indicate that TPA exerts its inhibitory action on BK responses at the sites of guanine nucleotide-binding protein or phospholipase C or both.
在神经母细胞瘤x胶质瘤杂交细胞NG108 - 15中，缓激肽（BK）受体刺激会导致磷酸肌醇水解、肌醇磷酸的形成以及细胞内钙的动员。用12 - O - 十四烷酰佛波醇13 - 乙酸酯（TPA）处理细胞可抑制细胞内钙浓度升高的峰值阶段。在放射性配体结合研究中，TPA处理并不干扰[3H]BK与完整细胞或细胞膜的特异性结合。鸟苷-5'-亚氨二磷酸将BK受体高亲和力位点转化为低亲和力位点的能力不受TPA影响。TPA处理显示出对BK刺激的肌醇三磷酸形成的剂量依赖性、非竞争性抑制。在经TPA处理的细胞的膜制剂中，鸟苷5' -（3 - O - 硫代）三磷酸刺激的肌醇三磷酸形成被抑制了50%。这些数据表明，TPA在鸟嘌呤核苷酸结合蛋白或磷脂酶C或两者的位点上对BK反应发挥其抑制作用。
