<Originals>Effect of endothelins on the fibrinogen-involved aggregation process in platelets of guinea pig

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The effects of endothelins (ETs) (-1,-2 & -3) on the platelet functions such as aggregation and ATP release have been examined with special reference to the intracellular free calcium level. In our experiments using platelets isolated from guinea pigs, all three members of the ET family showed a weak aggregation (3-7%) in platelet rich plasma (PRP) at high concentrations (10^<-8>-10^<-6>M). In the assay using washing platelets (WP) rinsed with Hepes buffer in the presence of fibrinogen, three peptides caused a more potent aggregation than in the assay using PRP without affecting the free calcium level, while no aggregation was observed by ET application in the absence of fibrinogen. In addition, each ET potentiated the aggregations induced by ADP (9 μM), collagen (10 μg/ml) or thrombin (0.3 U/ml) without any response to the intracellular free calcium. These findings indicate that ETs alone without fibrinogen hardly induce platelet aggregation directly, but may be involved in the modulation of the fibrinogen receptor-mediated aggregation in the presence of fibrinogen, associated with an increasing affinity between fibrinogen and platelet.
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