Paper| Volume 48, ISSUE 5, P535-548, December 01, 1987

Impaired thromboxane synthesis in preactivated human blood platelets: Agonist-specific, irreversible desensitization to thrombin

  • Hans-Joachim Reimers
    Veterans Administration Medical Center and Departments of Medicine (Division of Hematology) and Pathology, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA
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  • R.Kendall Baker
    Veterans Administration Medical Center and Departments of Medicine (Division of Hematology) and Pathology, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA
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  • J.Heinrich Joist
    Veterans Administration Medical Center and Departments of Medicine (Division of Hematology) and Pathology, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA
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      The causes for reduced platelet thromboxane synthesis in patients with acquired platelet storage pool disease are incompletely understood. The present study was designed to define the nature of the defect(s) underlying diminished thromboxane synthesis in human platelets previously exposed to thrombin in vitro. Platelets pretreated with high concentrations of thrombin were unable to form measurable amounts of thromboxane in response to a second stimulation with thrombin. In contrast, thrombin-pretreated platelets formed additional thromboxane in response to arachidonate, collagen, or A23,187. Thrombin pretreated platelets did not recover with respect to thrombin inducible thromboxane synthesis when incubated for two hours in plasma either in the presence or absence of added arachidonic acid. These observations suggest that neither inactivation of cyclooxygenase nor depletion of endogenous arachidonic acid is responsible for the impaired thrombin-induced thromboxane synthesis in thrombinprestimulated platelets. Impaired thrombin-induced thromboxane synthesis in these platelets may be due to agonist-specific, irreversible receptor uncoupling.


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