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Diacylglycerol and phorbol ester stimulate secretion without raising cytoplasmic free calcium in human platelets

Nature volume 305, pages 317–319 (1983)Cite this article

Abstract

An increase in cytoplasmic free calcium, [Ca2+]i, is thought to be the trigger for secretory exocytosis in many cells1–3. In blood platelets, large rises in [Ca2+]i can cause secretion4,5 and calcium has been regarded as the final common activator not only for secretion but also for shape-change and aggregation6,7. We have shown that while thrombin5 and platelet-activating factor (PAF)8 normally elevate [Ca2+]i, they can also stimulate shape-change and secretion even when the [Ca2+]i rise is suppressed. The present results strongly implicate diacylglycerol, produced by stimulus-dependent breakdown of phosphoinositide9–12, in this calcium-independent activation. Exogenous diacylglycerol activates a protein kinase (C-kinase) in platelets as do PAF, thrombin and collagen. 12-O-tetradecanoyl phorbol-13-acetate (TPA) also activates C-kinase13 and is a potent stimulus for secretion and aggregation14–16. It is shown here that the exogenous diacylglycerol 1-oleoyl-2-acetyl-glycerol (OAG) and TPA evoke similar secretion and aggregation without elevating [Ca2+]i above the basal level of 0.1 µM. The pattern of secretion resembles that produced by collagen and thrombin when [Ca2+]i remains at basal levels. Modest increases in [Ca2+]i, insufficient to stimulate secretion, markedly accelerate the responses to TPA and OAG.

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Authors and Affiliations

  1. Physiological Laboratory, Downing Street, Cambridge, CB2 3EG, UK

    T. J. Rink, A. Sanchez & T. J. Hallam

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  1. T. J. Rink
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  2. A. Sanchez
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  3. T. J. Hallam
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Rink, T., Sanchez, A. & Hallam, T. Diacylglycerol and phorbol ester stimulate secretion without raising cytoplasmic free calcium in human platelets. Nature 305, 317–319 (1983). https://doi.org/10.1038/305317a0

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