Is phosphatidic acid a calcium ionophore under neurohumoral control?
Is phosphatidic acid a calcium ionophore under neurohumoral control?
复制标题
磷脂酸是神经体液控制下的钙离子载体吗？
作者：
J. Putney;S. J. Weiss;C. Walle;R. A. Haddas
最近有新的兴趣在以前观察到的现象1，其中激素和神经递质改变32 P-磷酸盐的掺入率到磷脂，特别是磷脂酰肌醇（PI）和磷脂酸（PA）2。这源于Michell及其同事提出的理论，该理论假定这种“磷脂效应”在某种程度上与某些神经递质和激素激活膜Ca门的机制密切相关2 -5。然而，尽管Michell的观察结果与可能介于受体占据和Ca门控之间的磷脂参与是一致的，但它们并没有表明磷脂在Ca门控机制中的具体作用可能是什么。最近，Salmon和Honeyman证实6，关键事件可能是胰腺7、血小板8和平滑肌6、9中PI净分解后PA的净形成。PA在Pressman室中表现为钙离子载体10，因此，细胞膜中PA浓度的增加可能会增加这些膜的钙渗透性（另见参考文献5）。在大鼠腮腺中，与钙门控相关的受体（毒蕈碱、α-肾上腺素能和P物质）显示出磷脂效应，而β-肾上腺素能受体（作用于腺苷酸环化酶）则没有11，12。磷脂效应不依赖于钙离子，也不是由二价阳离子载体A23187产生的（参考文献11、12）。此外，该组织的一个容易量化的反应（K流出量测量为86 Rb的释放）绝对依赖于外部Ca的浓度（参考文献13），并通过推论，依赖于Ca流入的幅度14。我们在这里报告的证据表明，在磷脂效应的反应序列中形成的PA可能直接介导由表面膜受体激活引起的Ca向内运动。
There has recently been renewed interest in a previously observed phenomenon1 whereby hormones and neurotransmitters alter the rate of incorporation of 32P-phosphate into phospholipids, specifically, phosphatidylinositol (PI) and phosphatidic acid (PA)2. This has arisen from a theory formulated by Michell and coworkers which postulates that this ‘phospholipid effect’ is in some way intimately involved in the mechanism by which certain neurotransmitters and hormones activate membrane Ca gates2–5. However, although Michell's observations are consistent with a phospholipid involvement probably somewhere between receptor occupation and Ca gating, they do not suggest what the specific role of the phospholipids in the Ca gating mechanism might be. Recently, Salmon and Honeyman suggested6 that the critical event may be the net formation of PA following the net breakdown of PI which occurs in pancreas7, platelets8 and smooth muscle6,9. PA has been shown to behave as a Ca ionophore in a Pressman chamber10, and thus it is possible that an increase in PA concentration in cellular membranes might increase the Ca permeability of those membranes (see also ref. 5). In the rat parotid, receptors associated with Ca gating (muscarinic, α-adrenergic and substance P) show a phospholipid effect whereas β-adrenergic receptors (which act on adenylate cyclase) do not11,12. The phospholipid effect is Ca independent, and is not produced by the divalent cationophore A23187 (refs 11,12). Also, an easily quantifiable response of this tissue (K efflux measured as release of 86Rb) is absolutely dependent on the concentration of external Ca (ref. 13) and, by inference, on the magnitude of Ca influx14. We report here evidence suggesting that PA, which is formed during the reaction sequence of the phospholipid effect, may directly mediate the inward movement of Ca that results from activation of surface membrane receptors.