Suzuki R, Takenawa T
Department of Pharmacology, Tokyo Metropolitan Institute of Gerontology.
J Biochem. 1987 Sep;102(3):447-50. doi: 10.1093/oxfordjournals.jbchem.a122074.
Thyrotropin releasing hormone (TRH) caused significant breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) in GH3 cells, but vasoactive intestinal peptide (VIP) did not. However, VIP enhanced the TRH-induced hydrolysis of PIP2, the conversion of phosphatidylinositol 4-phosphate (PIP) to PIP2 and the accumulation of phosphatidic acid (PA). On the other hand, the tumor promoter, tetradecanoyl phorbol acetate (TPA), suppressed the TRH-induced hydrolysis of PIP2. In the membrane fraction, the addition of cAMP inhibited the PI kinase activity in a dose-dependent manner, but stimulated the PIP kinase activity. TPA did not affect the PI and PIP kinase activities at all. VIP enhanced the first spike phase of the TRH-induced increase in the intracellular Ca2+ level, while TPA inhibited such Ca2+ mobilization. These results suggested that cAMP-increasing agents enhanced inositol phospholipid metabolism and Ca2+ mobilization induced by TRH in GH3 cells but that TPA inhibited them.
促甲状腺激素释放激素（TRH）可导致GH3细胞中磷脂酰肌醇4,5-二磷酸（PIP2）的显著分解，但血管活性肠肽（VIP）则无此作用。然而，VIP可增强TRH诱导的PIP2水解、磷脂酰肌醇4-磷酸（PIP）向PIP2的转化以及磷脂酸（PA）的积累。另一方面，肿瘤促进剂十四酰佛波醇乙酸酯（TPA）可抑制TRH诱导的PIP2水解。在膜组分中，添加cAMP可剂量依赖性地抑制磷脂酰肌醇激酶（PI激酶）活性，但刺激磷脂酰肌醇4,5-二磷酸激酶（PIP激酶）活性。TPA对PI激酶和PIP激酶活性均无影响。VIP增强了TRH诱导的细胞内Ca2+水平升高的第一个尖峰相，而TPA则抑制这种Ca2+动员。这些结果表明，增加cAMP的试剂可增强TRH诱导的GH3细胞中肌醇磷脂代谢和Ca2+动员，但TPA则抑制它们。
