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The coumarin derivative AD6 inhibits the release of arachidonic acid by interfering with phospholipase A2 activity in human platelets stimulated with thrombin

  • Platelets and Thrombosis
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Abstract

AD6 is a coumarin derivative which is able to inhibit platelet aggregation and release due to various agonists as adrenaline, PAF, Ca++ ionophore and others. It has been demonstrated that this compound reduces the production of free arachidonate and diglyceride from human platelets pulse-labeled with radioactive arachidonic acid thus suggesting a possible interference with the activity of phospholipase A2 and/or phospholipase C. The present report indicates that the drug has no effect on the increase of the labeling of phosphatidic acid which takes place when platelets pulse-labeled with arachidonic acid are stimulated with thrombin. Furthermore, AD6 is not able to cause changes on the metabolism of phosphoinositides monitored using platelets pre-labeled with [3H] inositol. These observations exclude the possibility that AD6 interferes with phospholipase C activity. Experiments with platelets pulse-labeled with arachidonate suggest that AD6 inhibits phospholipase(s) A2 activity or modulate negatively one or more processes involved in its activation.

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Authors and Affiliations

  1. Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Università di Perugia, Perugia, Italy

    S. Porcellati, M. Stasi, R. Pistolesi & G. Goracci

  2. Istituto di Semeiotica Medica, Università di Perugia, Perugia, Italy

    V. Costantini & G. G. Nenci

  3. FIDIA Research Laboratories, Abano Terme, Italy

    M. Prosdocimi

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  1. S. Porcellati
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  7. G. Goracci
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Porcellati, S., Costantini, V., Prosdocimi, M. et al. The coumarin derivative AD6 inhibits the release of arachidonic acid by interfering with phospholipase A2 activity in human platelets stimulated with thrombin. Agents and Actions 29, 364–373 (1990). https://doi.org/10.1007/BF01966469

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