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|Titolo:||Activation of phospholipase A2 and B-thromboglobulin release in human platelets: comparative effects of thrombin and fluoroaluminate stimulation.|
|Autori interni:||STASI, Mario|
NENCI, Giuseppe Giorgio
|Data di pubblicazione:||1992|
|Rivista:||BIOCHIMICA ET BIOPHYSICA ACTA|
|Abstract:||Several reports have suggested that the activity of platelet phospholipase A2 is modulated by GTP-binding protein(s) whose nature and properties need to be defined. Fluoroaluminate is known to activate G-proteins and this leads to a number of cellular responses including the activation of phospholipases. This paper demonstrates that human platelets, prelabelled with [3H]arachidonic acid, produce free arachidonic acid when stimulated with fluoroaluminate and this effect is time- and dose-dependent. The production of arachidonic acid is not inhibited by neomycin, a PI-cycle inhibitor, but is completely abolished by mepacrine, an inhibitor of both phospholipase A2 and C. At low concentration of fluoroaluminate (10 mM NaF) phospholipase A2 but not phospholipase C is activated. In addition, fluoroaluminate treatment releases beta-thromboglobulin (beta-TG) and this effect is not inhibited by acetylsalicylic acid. Under identical conditions both neomycin and mepacrine suppress the release of arachidonic acid and beta-TG induced by thrombin. Sodium nitroprusside, which increases cGMP levels in platelets, inhibits arachidonic acid liberation and beta-TG release in thrombin-stimulated platelets but has no effect in fluoroaluminate-treated platelets; cGMP was reported to suppress phospholipase C activation. These results are consistent with the hypothesis that, in thrombin-stimulated platelets, the liberation of arachidonic acid and beta-TG are strictly dependent on the activation of phospholipase C. We have also provided evidence for the existence of a phospholipase A2 activated by a G-protein which is independent from the degradation of phosphoinositides and, contrary to phospholipase C, it is not down regulated by cGMP.|
|Appare nelle tipologie:||1.1 Articolo in rivista|
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