Letter | Published:

Is phosphatidic acid a calcium ionophore under neurohumoral control?


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.

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