Two 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 P2x-purinoceptor-mediated contractions in smooth muscle, was investigated for its antagonistic effects on adenosine diphosphate (ADP)-induced human platelet aggregation in platelet-rich plasma (PRP) and in washed platelets, respectively. Suramin served as reference compound. In PRP, suramin (1 mmol/l) was inactive whereas PPADS (1 mmol/l) considerably reduced the extent of aggregation. In contrast, both suramin (1 mmol/l) and PPADS (500 mumol/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 mumol/l) and suramin (0.1-1 mmol/l). Thus, in the present study washed platelets were more suited to detect an influence of PPADS and suramin as inhibitors of ADP-induced aggregation, and a delay of onset of aggregation was the most sensitive parameter in this regard. Comparing the effective threshold concentration of PPADS at P2x (1 mumol/l)- and the platelet P2t-purinoceptor, PPADS proves to be P2x-selective.