Abstract
An increase in the metabolism of phosphatidylinositol occurs in a wide variety of tissues by the action of specific ligands1–3. In platelets, the interaction of thrombin with its receptor initiates the degradation of phosphatidylinositol by the action of a specific phospholipase C (refs 4–8). In normal conditions of stimulation, the resultant 1,2-diacylglycerol is rapidly and completely phosphorylated to phosphatidic acid4–11. The formation of phosphatidic acid precedes the release of arachidonic acid from the phospholipids of stimulated platelets5. This early appearence of phosphatidate might result in the initial production of arachidonic acid and lysophosphatidic acid by the action of a phospholipase A2 specific for phosphatidate12. Phosphatidate/lysophosphatidate could induce calciumgating13–15 and subsequently stimulate phospholipases of the A2-type8, that degrade phosphatidylcholine, phosphatidyl-ethanolamine and a further fraction of phosphatidylinositol6. Alternatively, the lysophosphatidate produced may serve as a substrate for the transfer of arachidonate directly from other phospholipids16,17 to form new phosphatidate which in turn can release more arachidonate. Overall, such a sequence would be equivalent to phospholipase A2 activation of other phospholipids. Our present data indicate that when the release of arachidonic acid is completely inhibited by cyclic AMP or quinacrine, phosphatidic acid is redirected entirely to phosphatidylinositol and there is no production of arachidonate. In these conditions, the availability of calcium might be profoundly restricted. The correlation in platelets of a phosphatidylinositol by a specific phospholipase A2 might suggest that these phenomena are applicable to activations in other cell systems.
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Lapetina, E., Billah, M. & Cuatrecasas, P. The phosphatidylinositol cycle and the regulation of arachidonic acid production. Nature 292, 367–369 (1981). https://doi.org/10.1038/292367a0
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DOI: https://doi.org/10.1038/292367a0
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