REDUCTION IN THE NUMBER OF THROMBOXANE RECEPTORS ON HUMAN PLATELETS AFTER EXPOSURE TO GR32191

1 Exposure of human resuspended platelets in vitro for 30 min to the p otent thromboxane A2 (TP)-receptor blocking drug GR32191, followed by its removal by dilution-dissociation, reduced the degree of subsequent binding to 2 nM [H-3]-GR32191 by almost 50%. Exposure for longer peri ods (60 min) led to a further reduction. However, no change in the K(d ) of the radioligand was observed. 2 This effect of GR32191 could not be explained by persistent binding of drug to platelets since a diluti on-dissociation stage, designed to remove all drug, was included prior to measurement of binding. 3 Using an alternative TP-receptor radioli gand, [H-3]-SQ29,548, to monitor receptor number, a reduction in B(max ) was observed after GR32191 pre-treatment; the K(d) value of the radi oligand remained unchanged. 4 The effect was not a common property of TP-receptor blocking drugs since pre-exposure of platelets in vitro fo r 30 min to BM13.177 or SQ29,548 did not produce a fall in subsequent B(max) to [H-3]-SQ29,548. 5 While the mechanism behind this apparent d own-regulation of platelet TP-receptor is unknown, it may explain the long duration of action of GR32191 upon platelets in man which persist s in the absence of detectable drug in the plasma.