Ohsako S, Deguchi T
J Biol Chem. 1981 Nov 10;256(21):10945-8.
Phosphatidic acid added to the medium markedly elevated intracellular cyclic GMP content in cultured neuroblastoma N1E 115 cells. There was a significant elevation of cyclic GMP with 1 micrograms/ml and a maximum (70-fold) elevation with 100 micrograms/ml of phosphatidic acid. Other natural phospholipids did not increase, or increased only slightly, the cyclic GMP content in the cells. The elevation of cyclic GMP content by phosphatidic acid was absolutely dependent on extracellular calcium. Phosphatidic acid stimulated the influx of calcium into neuroblastoma cells 2- to 5-fold. The pattern of the calcium influx induced by phosphatidic acid was comparable to that of cyclic GMP elevation. The stimulation of calcium influx by phosphatidic acid was also observed in cultured heart cells, indicating that phosphatidic acid acts as a calcium ionophore or opens a specific calcium-gate in a variety of cell membranes. Treatment of neuroblastoma cells with phospholipase C increased 32Pi labeling of phosphatidic acid, stimulated the influx of calcium, and elevated the cyclic GMP content in the cells. Thus exogenous as well as endogenous phosphatidic acid stimulates the translocation of calcium across cell membranes and, as a consequence, induces the synthesis of cyclic GMP in the neuroblastoma cells.
添加到培养基中的磷脂酸显著提高了培养的神经母细胞瘤N1E 115细胞内的环鸟苷酸（cGMP）含量。1微克/毫升的磷脂酸可使cGMP显著升高，100微克/毫升的磷脂酸可使其达到最高（70倍）升高。其他天然磷脂不会增加或仅轻微增加细胞内的cGMP含量。磷脂酸引起的cGMP含量升高绝对依赖于细胞外钙。磷脂酸刺激钙流入神经母细胞瘤细胞的量增加2至5倍。磷脂酸诱导的钙流入模式与cGMP升高模式相当。在培养的心脏细胞中也观察到磷脂酸对钙流入的刺激作用，这表明磷脂酸在多种细胞膜中充当钙离子载体或打开特定的钙通道。用磷脂酶C处理神经母细胞瘤细胞可增加磷脂酸的32Pi标记，刺激钙流入，并提高细胞内的cGMP含量。因此，外源性和内源性磷脂酸均刺激钙跨细胞膜的转运，结果诱导神经母细胞瘤细胞中环鸟苷酸的合成。
