Prostacyclin Receptors on Human Platelets

Prostacyclin (PG12) is the most potent endogenous inhibitor of platelet aggregation. Prostacyclin increases platelet cyclic AMP concentration by activating a receptor on the platelet cell membrane. The characteristics of this receptor have been studied in fractured human platelets from normal subjects by measuring specific binding of tritiated prostacyclin (Blair, Hensby & MacDermot, 1981, Journal of Labelled Compounds and Radiopharmaceuticals, 18, 361-370). by Scatchard analysis, one of high affinity and one of low affinity. Measured at equilibrium, the dissociation constant of the high affinity site was 12 IIM which is similar to that described in whole human platelets (Siegl, Smith, Silver, Nicolaou & Ahern, 1979, Journal of Clinical Investigation 63, 215-220). There was a mean of 2.4 x lo9 high affinity receptors per platelet. Time course experiments defined the rate constant for the forward reaction k+l as 3 x 10-5 M-1 sec-1 and the rate constant for the dissociation of the lfgand receptor complex k-l as 2.9 x 10-3 sec-1. constant k-l/k+l was 9.6 nM. Prostaglandin El CPGE1) and PGI2'apparently compete for the same high affinity receptor but the affinity for PGI2 is 40 times greater than that for PGE1. If FG12 is a circulating hormone then compensatory up-regulation of platelet prostacyclin receptors might be associated with conditions where deficiency of vascular prostacyclin production has been proposed, such as diabetes (Dollery, Friedman, Aensby, Kohner, Lewis, Porta & Webster 1979, Lancet, 11, 1365), atheroma (Sinzinger, Feigl & Silberbauer, 1979, Lancet, 11, 469) and pre-eclampsia (Downing, Shepherd 8 Lewis, 1980, Lancet, 11, 1374). Two binding sites were identified