Kato H, Ishitoya J, Takenawa T
Biochem Biophys Res Commun. 1986 Sep 30;139(3):1272-8. doi: 10.1016/s0006-291x(86)80315-1.
Cyclic AMP-increasing agents such as PGE2 and dibutyryl cAMP inhibited the fMLP-induced inositol phospholipids metabolism mainly through the suppression of the conversion of phosphatidylinositol(PI) to phosphatidylinositol 4,5-bisphosphate(PIP2). A part of this inhibition was found to be caused by the inhibitory effect of cAMP on PI kinase using isolated plasma membranes. On the other hand, 12-O-tetradecanoyl phorbol acetate(TPA) mainly inhibited the conversion of phosphatidylinositol 4-phosphate(PIP) to PIP2 without a significant effect on the fMLP-induced breakdown of PIP2, though direct effect of TPA on PI and PIP kinases was not demonstrated in isolated plasma membranes. Concerning Ca2+ mobilization, both cAMP-increasing agents and TPA inhibited the fMLP-induced second phase of Ca2+ elevation, while they did not affect the first phase of Ca2+ rapid increase. However, Ca2+ ionophore ionomycin-induced Ca2+ elevation was only inhibitable by TPA but not PGE2. These results suggest that cAMP inhibits the fMLP-induced Ca2+ influx, while TPA stimulates Ca2+ removal from cytosol.
环磷酸腺苷（cAMP）增加剂，如前列腺素E2（PGE2）和二丁酰环磷酸腺苷（dibutyryl cAMP），主要通过抑制磷脂酰肌醇（PI）向磷脂酰肌醇4,5-二磷酸（PIP2）的转化来抑制甲酰甲硫氨酸-亮氨酸-苯丙氨酸（fMLP）诱导的肌醇磷脂代谢。利用分离的质膜发现，这种抑制作用部分是由cAMP对PI激酶的抑制作用引起的。另一方面，12-O-十四酰佛波醇-13-乙酸酯（TPA）主要抑制磷脂酰肌醇4-磷酸（PIP）向PIP2的转化，而对fMLP诱导的PIP2分解没有显著影响，尽管在分离的质膜中未证明TPA对PI和PIP激酶有直接作用。关于钙离子动员，cAMP增加剂和TPA均抑制fMLP诱导的钙离子升高的第二阶段，而它们不影响钙离子快速增加的第一阶段。然而，钙离子载体离子霉素诱导的钙离子升高仅可被TPA抑制，而不能被PGE2抑制。这些结果表明，cAMP抑制fMLP诱导的钙离子内流，而TPA刺激钙离子从细胞质中移除。
