Rapid decrease of phosphatidylinositol 4,5-bisphosphate in thrombin-stimulated platelets.

We have examined the earlychanges of the polyphosphoinositides in stimulated platelets.Our resultsshow that a sharp decrease itnhe content of phosphatidylinositol 4,5-bisphosphate precedes the increased incorporation of,'"Pinto polyphosphoinositides.This

M M Billah; E G Lapetina

2021

Scholarcy highlights

  • We have examined the earlychanges of the polyphosphoinositides in stimulated platelets.Our resultsshow that a sharp decrease itnhe content of phosphatidylinositol 4,5-bisphosphate precedes the increased incorporation of,'"Pinto polyphosphoinositides.This
  • Ionophore A23187 was from Eli L a y
  • 2. "'P-labeled platelets were incubated for 10 s with different concentrations of thrombin.Thecontrolvaluesfor,'?P radioactivity for phosphatidylinositol 4,5-bisphosphate andphosphatidylinositol 4-monophosphate were 161,000 f 1,500 and 62,000 k 1,000, respectively
  • Thepresentinformation clearly indicatesthatthrombin stimulation of horseplatelets inducesa rapiddecrease of phosphatidylinositol 4,5-bisphosphate. This earlyloss is transient and precedes the known increased incorporation of '"P into phosphatidylinositol 4,5-bisphosphate. This initial loss of phosphatidylinositol 4,5-bisphosphate appears to beinsensitive to increased levels of cytosolic Ca2+ since ionophore A23187 is ineffective in inducingthis effect
  • Phosphatidylinositol 4,5-bisphosphatemight be cleaved by a phosphodiesterase activity to 1,2-diacylglycerol; as studies in brain and in erythrocytes indicate that this enzyme has an absolute requiremefonrtCa"', it is unlikely that this enzymatic activityis related to theloss of phosphatidylinositol4,5-bisphosphatein platelets because, inour present experiments, the mobilization of cytosolic Ca2+ by ionophore A23187 does not induce the loss
  • Such enhanced levels ofCa" could, in turn, activate enzymatic activities, such as phospholipases Ap, which require higher concentrations of Ca'+ than phospholipase C . we do not have definitive proof of these propositions, the present results arseuggestive of an important role for the initial decrease of phosphatidylinositol 4,5-bisphosphate in the initiation of platelet activation, presumably by effecting early mobilization of free Ca2+

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