2 DIFFERENT INHIBITORY EFFECTS OF PYRIDOXALPHOSPHATE-6-AZOPHENYL-2',4'-DISULFONIC ACID ON ADENOSINE DIPHOSPHATE-INDUCED HUMAN PLATELET-AGGREGATION

In the present study the novel compound pyridoxalphosphate-6-azophenyl -2',4'-disulfonic acid (PPADS), which has been shown to inhibit P-2x-p urinoceptor-mediated contractions in smooth muscle, was investigated f or its antagonistic effects on adenosine diphosphate (ADP)-induced hum an platelet aggregation in platelet-rich plasma (PRP) and in washed pl atelets, respectively. Suramin served as reference compound. In PRP, s uramin (1 mmol/l) was inactive whereas PPADS (1 mmol/l) considerably r educed the extent of aggregation. In contrast, both suramin (1 mmol/l) and PPADS (500 mu mol/l) markedly depressed the aggregation of washed platelets. In addition, there was a peculiarity in washed platelets: a delay of onset of platelet aggregation up to 15 min in the presence of PPADS (10-500 mu mol/l) and suramin (0.1-1 mmol/l). Thus in the pre sent study washed platelets were more suited to detect an influence of PPADS and suramin as inhibitors of ADP-induced aggregation, and a del ay of onset of aggregation was the most sensitive parameter in this re gard. Comparing the effective threshold concentration of PPADS at P-2x (mu mol/l)- and the platelet P-2t-purinoceptor, PPADS proves to he P- 2x-selective.