Species-dependent Specificity of Platelet Aggregation Inhibitors from Snake Venom

Echistatin, flavoridin and kistrin belong to a family of low molecular weight snake-venom proteins, termed “disintegrins” because of their ability to bind integrin receptors on the cell surfaces. Most disintegrins contain the tripeptide arginine-glycine-aspartic acid (RGD) sequence, which represents a common cell adhesion recognition site. Here we report the differing activity of echistatin, flavoridin and kistrin on adenosine 5′-diphosphate (ADP)-induced aggregation of platelets from the buffalo, dog and horse. The three disintegrins inhibited the aggregation of platelets from all three animal species at nanomolar concentrations. Echistatin was the most active of the disintegrins towards equine platelets, but flavoridin and kistrin showed a higher potency than echistatin in inhibiting aggregation of platelets from the buffalo and dog. Kistrin was 1·6-fold more effective than flavoridin in inhibiting ADP-induced aggregation of platelets from either the buffalo or dog, whereas flavoridin was 2·1-fold more active than kistrin in inhibiting aggregation of equine platelets. The species-dependent platelet sensitivity to these snake-venom proteins may reflect structural differences of the integrin receptor GP IIb/IIIa on the platelet surface in different mammalian species.