Staurosporine induces hydrolysis of phosphatidyl inositol 4,5-bisphosphate in human platelets.
Staurosporine in the micromolar range raised inositol trisphosphate in intact human platelets to levels comparable to that mediated by thrombin. This response was inhibited by neomycin, a phospholipase C antagonist. Staurosporine alone induced a weak, transient rise in cytosolic free calcium levels ([Ca2+]i) from release of internal Ca2+ stores but potentiated the effect induced by thrombin. Therefore, it is unlikely that this alkaloid suppressed inositol trisphosphate mobilization of Ca2+. Additional studies show that staurosporine, 0.5-5 microM, stimulated GTPase activity in platelet membranes while 2 microM K252a and 20 microM H7 were inactive. Present results suggest that staurosporine may activate platelet phospholipase C at the level of G proteins or receptors.
Turkson
J
J
Department of Pharmacology and Therapeutics, University of Calgary, Alberta, Canada.
Li
X B
XB
Wong
K
K
D000470:Alkaloids / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D066298:In Vitro Techniques; D008345:Manganese / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D019311:Staurosporine; D010738:Type C Phospholipases / Q000378:metabolism
D000470:Alkaloids; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D008345:Manganese; D010738:Type C Phospholipases; D019311:Staurosporine; D002118:Calcium