EXPRESSION OF ADHESION MOLECULES ON THE SURFACE OF ACTIVATED PLATELETS IS DIMINISHED BY PGI(2) ANALOGS AND AN NO (EDRF) DONOR - A COMPARISON BETWEEN PLATELETS OF HEALTHY AND DIABETIC SUBJECTS

Adhesion molecules such as P-selectin (CD 62), glycoprotein (GP) 53(CD 63) and thrombospondin play a decisive role in the thrombogenic transf ormation of platelets. Here we present evidence obtained using flow cy tometric analysis that the PGI(2)-mimetics iloprost and taprostene, an d an NO (EDRF)-donor (SIN-1) are able to inhibit the expression of P-s electin, GP 53 and thrombospondin on human platelets activated by subm aximal concentrations of thrombin. Since the half-maximal concentratio ns for inhibition of antigen expression (0.15 nM for iloprost, 3.0-5.3 nM for taprostene) are much lower than for activation of adenylate cy clase (1.4 nM for iloprost and 29.4 nM for taprostene) our data sugges t that the occupation of a small number of PGI(2)-receptors is suffici ent to inhibit the thrombogenic transformation and that spare PGI(2)-r eceptors are present on human platelets. In diabetes, the EC(50) for i nhibition of expression of platelet antigens is shifted to higher conc entrations suggesting that platelets from type 1 diabetic patients are partly resistant to PGI(2). Since the dose dependent increase in c-AM P by iloprost is not changed and intraplatelet c-AMP is elevated in pl atelets of diabetic patients, we assume that steps in the activation c ascade subsequent to activation of adenylate cyclase are disturbed in diabetes.