Heparin does not interfere with prostacyclin and prostaglandin D2 binding to platelets

Heparin has been reported to antagonize the platelet antiaggregating activity of prostacyclin (PGI₂) and prostaglandin D₂(PGD₂). To investigate whether heparin interferes with PGI₂ and/or PGD₂ binding to the specific membrane platelet receptors, the number and the affinity of binding sites for tritiated PGI₂and PGD₂ were determined in 8 healthy subjects (aged 25-32; 4 for PGI₂ and 4 for PGD₂studies) in the absence and in the presence of heparin. Preliminary aggregation tests indicated that the heparin concentration tested (2 I.U./ml) reduced the antiaggregating activity of PGI₂ and PGD₂. Heparin,when preincubated with platelet suspension, did not induce any significant change in the number/platelet (bs/plt) and affinity (Kd) of PGI₂ and PGD₂ binding sites (bs) in comparison to control values (PGI₂ high affinity bs: bs/plt=106±12 vs 107±17 - Kd=9.7±3.1 vs 10.0±2.3 nM; PGI₂ low affinity bs: bs/ptt=3551±233 vs 3670±465 - Kd=877±125±125 vs 833±104 nM; PGD₂ bs: bs/plt-228±14 vs 234±24 - Kd=68±10 vs 73±7 nM; p>0.4 for all the differences). No significant binding modification was also observed when heparin was preincubated with ³H-PGI₂ and 3H-PGD₂. The present demonstration that heparin does not interfere with PGI₂ and PGD₂ binding to platelets is consistent with the hypothesis that heparin reduces the antiaggregating effects of PGI₂ and PGD₂ by directly potentiating platelet aggregation.