Abstract
Stimulation of platelets by collagen results in increased formation of the polyphosphoinositides, phosphatidylinositol phosphate (PtdInsP) and phosphatidylinositol bisphosphate (PtdInsP 2) through stimulation of phosphoinositide kinase activities. We investigated a possible regulatory role of endogenous thromboxane formation and protein kinase C (PKC) activation in the induction of phosphoinositide phosphorylation following collagen stimulation, as well as following stimulation by the thromboxane mimetic, U-46619. Human platelets were prelabeled with [3H]inositol and stimulated with collagen (2 μg/mL) or U-46619 (1 μM), in the absence or presence of either the cyclo-oxygenase/lipoxygenase inhibitor, BW755C, or staurosporine, a putative inhibitor or PKC. Collagen stimulation resulted in a time-dependent increase in [3Hinositol-labeled PtdInsP and PtdInsP 2 which was completely inhibited in the presence of BW755C. Addition of U-46619 to BW755C-treated, collagen-stimulated platelets restored the increased polyphosphoinositide formation. Stimulation of platelets with U-46619 alone also resulted in increased formation of [3H]PtdInsP and [3H]PtdInsP 2, but this was not affected by the presence of BW755C. These results suggest that the collagen-induced activation of phosphoinositide kinases was dependent upon thromboxane formation, but that U-46619-induced phosphoinositide formation was rather independent of further thromboxane production. Pretreatment of platelets with staurosporine, prior to agonist addition, completely blocked the collagen-stimulated rise in radiolabeled PtdInsP and the U-46619-induced PtdInsP and PtdInsP 2 generations, suggesting that protein kinase, possibly PKC, may play a role in the activation of phosphoinositide kinases by these agonists.
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Abbreviations
- ANS:
-
8-anilino-1-naphthalenesulfonic acid
- BW755C:
-
3-amino-1-(3-trifluromethylphenyl)-2-pyrazoline
- lysoPtdIns:
-
lysophosphatidylinositol
- PKC:
-
protein kinase C
- PtdIns:
-
phosphatidylinositol
- PtdInsP :
-
phosphatidylinositol phosphate
- PdtInsP 2 :
-
phosphatidylinositol bisphosphate
- U-46619:
-
9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α
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Thomas, L.M., Holub, B.J. BW755C or staurosporine inhibits collagen-stimulated phosphoinositide phosphorylation in platelets. Lipids 26, 689–695 (1991). https://doi.org/10.1007/BF02535615
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DOI: https://doi.org/10.1007/BF02535615