ADP INDUCES DESENSITIZATION OF EQUINE PLATELET-AGGREGATION RESPONSES - STUDIES USING ADP-BETA-S, A STABLE ANALOG OF ADP

Pre-incubation of equine platelets in platelet-rich plasma with adenosine 5'-diphosphate (ADP) induced a reduction in aggregation responsiveness to subsequent additions of ADP. The desensitisation was shown to be homologous since the responsiveness to platelet-activating factor, thrombin, collagen, 5-hydroxytryptamine or ionomycin remained unchanged. Adenosine 5'-(beta-thio)-diphosphate (ADPbetaS), a non-hydrolysable analogue of ADP, was shown to act as an agonist inducing aggregation by interaction with the ADP receptor. ADPbetaS was then used in the desensitisation studies in which residual ADP was degraded by the addition of apyrase. The desensitisation to ADPbetaS fully recovered by one hour after pre-treatment with ADP and was not induced by an extracellular mediator. The mechanism of desensitisation is therefore likely to involve the ADP receptor or proximal intermediates in the signal transduction pathway for ADP.