Inhibition of induced and spontaneous platelet aggregation by destabilase from medicinal leech

Destabilase, endo-epsilon-(gamma-Glu)-Lys isopeptidase from the medicinal l eech, inhibits arterial thrombus formation in rats. Inhibition of platelet aggregation was supposed to be one of the main mechanisms of this phenomeno n. To elucidate this question highly purified destabilase preparations were used. Aggregation was monitored both by a turbidometric method and by a me thod based on real-time estimation of mean aggregate size. Spontaneous aggr egation of human platelets was completely blocked by destabilase. At 5 mu M ADP maximal inhibition was 63%. Aggregation induced by PAF (100 nM) and co llagen (0.1 mg/ml) was inhibited in the presence of destabilase by 50 and 6 5%, respectively. This enzyme does not activate adenylate cyclase but inhib its it. We suggest that destabilase interacts with high-affinity binding si tes on the platelet plasma membrane, thus providing an anti-aggregating eff ect. This idea coincides with the data that destabilase primary structure h as high homology with some adhesive proteins.