| Abstrakt: |
Equine platelets, when treated with the anthelmintic drug diethylcarbamazine (DEC), gave a dose-dependent release of radiolabeled serotonin without concomitant aggregation. At levels of the drug that gave only minimal release of radiolabel, marked dose-dependent inhibition of platelet aggregation to three of four platelet agonists tested--adenosine diphosphate (ADP), collagen, and arachidonic acid--was observed. With ADP, inhibition was observed to be reversed by removal of DEC prior to agonist challenge. However, with collagen, inhibition was only partially reduced by prior removal of DEC; whereas with arachidonate the DEC inhibition appeared not to be reduced by removal of the drug. Thrombin-induced aggregation was not inhibited by DEC. DEC therefore has the heretofore unrecognized property of modulating platelet function to several platelet agonists as well as inducing the platelet release of serotonin. Our results would suggest a reversible membrane-drug interaction as the potential site of modulation for ADP and collagen, whereas an apparent irreversible inhibition is suggested for arachidonate-induced aggregation. |
