Compounds > inositol-1-4-5-trisphosphate

inositol-1-4-5-trisphosphate and Hemorrhagic-Disorders

inositol-1-4-5-trisphosphate has been researched along with Hemorrhagic-Disorders* in 1 studies

Other Studies

1 other study(ies) available for inositol-1-4-5-trisphosphate and Hemorrhagic-Disorders

Article	Year
Human platelet signaling defect characterized by impaired production of inositol-1,4,5-triphosphate and phosphatidic acid and diminished Pleckstrin phosphorylation: evidence for defective phospholipase C activation. Blood, 1996, Sep-01, Volume: 88, Issue:5 Signal transduction on platelet activation involves phosphoinositide-specific phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositides and formation of inositol-1,4,5-triphosphate [I(1,4,5)P3], which mediates Ca2+ mobilization, and diacylglycerol (DG), which activates protein kinase C (PKC) to phosphorylate a 47-kD protein (Pleckstrin). We studied these events in two related patients previously reported (Blood 74:664, 1989) to have abnormal aggregation and 14C-serotonin secretion, and impaired intracellular Ca2+ mobilization in response to several agonists. Thrombin-induced I(1,4,5)P3 and phosphatidic acid formation were diminished. Pleckstrin phosphorylation was impaired on activation with thrombin, platelet-activating factor, and ionophore A23187, but was normal with PKC activator 1,2-dioctonyl-sn-glycerol (DiC8). Ca2+ mobilization induced by guanosine triphosphate (GTP) analog guanosine 5'-0-(3 thiotriphosphate) (GTP gamma S) was diminished. Pretreatment with either A23187 or DiC8 did not correct the impaired adenine diphosphate-induced secretion; however, upon stimulation with A23187 plus DiC8, pleckstrin phosphorylation and secretion were normal, indicating that both PKC activation and Ca2+ mobilization are essential for normal secretion. We conclude that these patients have a unique inherited platelet defect in formation of two key intracellular mediators [I(1,4,5)P3 and DG] and in the responses mediated by them due to a defect in postreceptor mechanisms of PLC activation. Topics: Adenosine Diphosphate; Adult; Blood Platelets; Blood Proteins; Calcimycin; Calcium; Diglycerides; Enzyme Activation; Female; Hemorrhagic Disorders; Humans; Inositol 1,4,5-Trisphosphate; Male; Middle Aged; Myosin Light Chains; Phosphatidic Acids; Phosphatidylinositol Diacylglycerol-Lyase; Phosphoproteins; Phosphoric Diester Hydrolases; Phosphorylation; Platelet Activating Factor; Platelet Aggregation; Protein Processing, Post-Translational; Serotonin; Signal Transduction; Thrombin	1996

Article

Year

Human platelet signaling defect characterized by impaired production of inositol-1,4,5-triphosphate and phosphatidic acid and diminished Pleckstrin phosphorylation: evidence for defective phospholipase C activation.

Blood, 1996, Sep-01, Volume: 88, Issue:5

Signal transduction on platelet activation involves phosphoinositide-specific phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositides and formation of inositol-1,4,5-triphosphate [I(1,4,5)P3], which mediates Ca2+ mobilization, and diacylglycerol (DG), which activates protein kinase C (PKC) to phosphorylate a 47-kD protein (Pleckstrin). We studied these events in two related patients previously reported (Blood 74:664, 1989) to have abnormal aggregation and 14C-serotonin secretion, and impaired intracellular Ca2+ mobilization in response to several agonists. Thrombin-induced I(1,4,5)P3 and phosphatidic acid formation were diminished. Pleckstrin phosphorylation was impaired on activation with thrombin, platelet-activating factor, and ionophore A23187, but was normal with PKC activator 1,2-dioctonyl-sn-glycerol (DiC8). Ca2+ mobilization induced by guanosine triphosphate (GTP) analog guanosine 5'-0-(3 thiotriphosphate) (GTP gamma S) was diminished. Pretreatment with either A23187 or DiC8 did not correct the impaired adenine diphosphate-induced secretion; however, upon stimulation with A23187 plus DiC8, pleckstrin phosphorylation and secretion were normal, indicating that both PKC activation and Ca2+ mobilization are essential for normal secretion. We conclude that these patients have a unique inherited platelet defect in formation of two key intracellular mediators [I(1,4,5)P3 and DG] and in the responses mediated by them due to a defect in postreceptor mechanisms of PLC activation.

Topics: Adenosine Diphosphate; Adult; Blood Platelets; Blood Proteins; Calcimycin; Calcium; Diglycerides; Enzyme Activation; Female; Hemorrhagic Disorders; Humans; Inositol 1,4,5-Trisphosphate; Male; Middle Aged; Myosin Light Chains; Phosphatidic Acids; Phosphatidylinositol Diacylglycerol-Lyase; Phosphoproteins; Phosphoric Diester Hydrolases; Phosphorylation; Platelet Activating Factor; Platelet Aggregation; Protein Processing, Post-Translational; Serotonin; Signal Transduction; Thrombin

1996