Inhibition of aggregation of rabbit and human platelets induced by adrenaline and 5‐hydroxytryptamine by KB‐R7943, a Na + /Ca 2+ exchange inhibitor

We investigated the effect of KB‐R7943, a Na + /Ca 2+ exchange inhibitor, on the aggregation response induced by adrenaline and 5‐hydroxytryptamine (5‐HT), alone or in combination in human and rabbit platelets in the presence or absence of ouabain. KB‐R7943 inhibited aggregation induced by the combination of adrenaline and 5‐HT in a concentration‐dependent manner. The IC 50 values of KB‐R7943 were 4.2±2.0 or 3.0±0.7 μ M with washed rabbit platelets with or without ouabain pretreatment, respectively. In platelet‐rich human plasma, the aggregation was biphasic. The IC 50 value of KB‐R7943 was 17.2±4.4 μ M for the first phase aggregation. KB‐R7943 did not inhibit the first phase of aggregation induced by adrenaline alone, or the monophasic aggregation induced by 5‐HT alone. The aggregation of rabbit platelets depended on the presence of K + in the medium, and K + ‐dependent and K + ‐independent Ca 2+ influx were observed in resting platelets. Ouabain treatment increased only the K + ‐dependent but not the K + ‐independent Ca 2+ influx. KB‐R7943 inhibited K + ‐dependent Ca 2+ influx with or without ouabain pretreatment, but not K + ‐independent Ca 2+ influx. From these results, we conclude that KB‐R7943 inhibits the adrenaline plus 5‐HT induced aggregation of rabbit and human platelets by inhibiting K + ‐dependent Na + /Ca 2+ exchange (NCKX). Our results suggest that NCKX plays an important role in platelet aggregation.British Journal of Pharmacology (2001) 132 , 1383–1388; doi: 10.1038/sj.bjp.0703928