DEFICIENCY OF (P-33)2MES-ADP BINDING-SITES ON PLATELETS WITH SECRETION DEFECT, NORMAL GRANULE STORES AND NORMAL THROMBOXANE A(2) PRODUCTION- EVIDENCE THAT ADP POTENTIATES PLATELET SECRETION INDEPENDENTLY OF THE FORMATION OF LARGE PLATELET AGGREGATES AND THROMBOXANE A(2) PRODUCTION

By the term ''Primary Secretion Defect'' (PSD), we mean a common heter ogeneous group of congenital defects of platelet secretion, characteri zed by a normal primary wave of platelet aggregation induced by ADP an d other agonists, a normal concentration of platelet granule contents, and normal production of thromboxane A(2). The biochemical abnormalit ies responsible for PSD are not well known. Since a secretion defect s imilar to PSD is found in platelets that are severely deficient of bin ding sites for the ADP analogue 2MeS-ADP and do not aggregate in respo nse to ADP, we tested the hypothesis that PSD platelets have moderatel y decreased 2MeS-ADP binding sites, which may be sufficient for normal ADP-induced aggregation but not for potentiating platelet secretion. The specific binding of [P-33]2MeS-ADP to platelets from 3 PSD patient s (347, 443 and 490 sites/platelet; KD 2.8-3.9 nM) was lower than to p latelets from 24 normal subjects (647 [530-1102]; KD = 3.8 [2.3-7.3]) (median [range]). Normal values were found in a fourth PSD patient (71 0; KD 3.7). The degree of inhibition of PGE1-induced cAMP increase by 0.1 mu M ADP was lower in patients than in controls. The secretion ind uced by the endoperoxide analogue U46619 from normal? acetylsalicylic acid-treated platelets under conditions that prevented the formation o f large aggregates was potentiated by 1 mu mol/l ADP and inhibited by apyrase. These findings indicate that a partial deficiency of the plat elet ADP receptor(s) might be responsible for the defect of platelet s ecretion in some PSD patients and that ADP potentiates platelet secret ion independently of the formation of large aggregates and thromboxane A(2) production.