Hamamori Y, Hoshijima M, Ohmori T, Ueda T, Takai Y
Department of Biochemistry, Kobe University School of Medicine, Japan.
Cancer Res. 1988 Dec 1;48(23):6697-702.
Calf serum induced the phospholipase C-mediated hydrolysis of phosphoinositides in normal rat kidney (NRK) cells transformed by a temperature-sensitive Kirsten murine sarcoma virus (tsK-NRK cells). Various growth factors known to induce the phospholipase C reactions in other cell types, such as platelet-derived growth factor, fibroblast growth factor, epidermal growth factor, thrombin, vasopressin, bombesin, cholecystokinin, and prostaglandin F2 alpha, did not induce phospholipase C reactions in the transformed NRK cells. Furthermore, noradrenaline, histamine, dopamine, angiotensin II, carbachol, and tumor growth factor-beta did not induce phospholipase C reactions. However, serotonin did induce phospholipase C reactions. The amount of serotonin contained in the calf serum was sufficient to support 50% of the activity promoted by the serum itself, and calf serum-induced phospholipase C reactions were inhibited to 10-20% of the original level by ketanserin and methysergide, known to be antagonists for the serotonin receptors. Dialysis almost completely removed serotonin from calf serum and reduced the serum-induced phospholipase C reactions. Moreover, the phospholipase C reactions induced by calf serum and serotonin were inhibited by pretreatment of the cells with pertussis toxin or 12-O-tetradecanoylphorbol-13-acetate. These results indicate that serotonin is one of the major serum factors inducing phospholipase C-mediated hydrolysis of phosphoinositides in transformed NRK cells. Serotonin induced phospholipase C reactions not only in tsK-NRK cells but also in nontransformed NRK cells. However, serotonin did not induce these reactions in Swiss 3T3 cells or NIH 3T3 cells.
小牛血清可诱导由温度敏感型 Kirsten 鼠肉瘤病毒转化的正常大鼠肾（NRK）细胞（tsK-NRK 细胞）中磷脂酶 C 介导的磷酸肌醇水解。各种已知能在其他细胞类型中诱导磷脂酶 C 反应的生长因子，如血小板衍生生长因子、成纤维细胞生长因子、表皮生长因子、凝血酶、血管加压素、蛙皮素、胆囊收缩素和前列腺素 F2α，在转化的 NRK 细胞中均不诱导磷脂酶 C 反应。此外，去甲肾上腺素、组胺、多巴胺、血管紧张素 II、卡巴胆碱和肿瘤生长因子-β也不诱导磷脂酶 C 反应。然而，血清素确实能诱导磷脂酶 C 反应。小牛血清中所含血清素的量足以支持血清本身所促进活性的 50%，并且小牛血清诱导的磷脂酶 C 反应被已知为血清素受体拮抗剂的酮色林和甲基麦角新碱抑制至原始水平的 10 - 20%。透析几乎完全从小牛血清中去除了血清素，并降低了血清诱导的磷脂酶 C 反应。此外，用百日咳毒素或 12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯预处理细胞可抑制小牛血清和血清素诱导的磷脂酶 C 反应。这些结果表明，血清素是诱导转化的 NRK 细胞中磷脂酶 C 介导的磷酸肌醇水解的主要血清因子之一。血清素不仅在 tsK - NRK 细胞中诱导磷脂酶 C 反应，在未转化的 NRK 细胞中也能诱导。然而，血清素在 Swiss 3T3 细胞或 NIH 3T3 细胞中不诱导这些反应。
