Benzodiazepine analogues inhibit arachidonate-induced aggregation and thromboxane synthesis in human platelets. |
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| Authors: | P. Fonlupt M. Croset M. Lagarde |
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| Affiliation: | Unité INSERM 205-Laboratoire de Chimie Biologique, Villeurbanne, France. |
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| Abstract: | 1. Benzodiazepine analogues inhibit human platelet aggregation induced by arachidonate with an EC50 value of 0.68 microM for PK 11195, the most potent analogue used. 2. There was a highly significant correlation between the inhibition of arachidonate-induced aggregation and the affinity for the peripheral-type of benzodiazepine binding sites. 3. There was no significant correlation between the inhibition of the platelet activating factor (PAF)-induced aggregation and the binding to the peripheral-type of benzodiazepine binding sites. 4. The inhibition of platelet aggregation seems to result from the inhibition of arachidonic acid cyclo-oxygenation, since the synthesis of thromboxane and 12-hydroxy-heptadecatrienoic acid, both cyclo-oxygenase products, was reduced. 5. Our results suggest that peripheral-type of benzodiazepine binding sites on human platelets could be linked to cyclo-oxygenase. |
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