Phosphatidylinositol 4,5-bisphosphate may represent the site of release of plasma membrane-bound calcium upon stimulation of human platelets.
Thrombin stimulation of human blood platelets caused an extensive (up to 45%) and rapid (5-10 s) decline in endogenous phosphatidylinositol 4,5-bisphosphate (PI-P2). Thrombin initiated an equally rapid loss of membrane-bound Ca, as indicated by the decrease in fluorescence of chlortetracycline (CTC)-loaded platelets. PI-P2 breakdown also correlated with decreased CTC fluorescence upon use of other platelet stimuli: Arachidonate caused moderate and slow decreases in both PI-P2 and CTC fluorescence, while ionophore only induced minimal changes. Thrombin-induced decreases in PI-P2 content could account for release of sufficient membrane-bound Ca to raise cytoplasmic free [Ca2+] to 1-2 microM, supporting the hypothesis that PI-P2 represents the Ca-binding site involved in the stimulus-dependent increase in cytoplasmic Ca2+ evoked by receptor-ligand interactions.
D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000097:blood*; D013050:Spectrometry, Fluorescence; D013917:Thrombin / Q000494:pharmacology
D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D013917:Thrombin; D002118:Calcium