Inhibition of platelet aggregation and endogenous lectin activity by oligoamines

Abstract

Amino sugars and basic amino acids inhibit platelet aggregation and the activity of the endogenous platelet lectin, yet,relatively high concentrations(∼ 30 mM) are required for the inhibition. If cooperative interactions are involved in these platelet surface activities, oligomers of primary amines should be more potent inhibitors than their individual component amines. Accordingly, series of oligomers of basic amino acids,of the polyamines (putrescine, spermidine and spermine) and of aliphatic diamines differing in chain length were tested for potency of inhibition of platelet aggregation and endogenous platelet lectin activity. Indeed,oligoamines were much more potent inhibitors of platelet aggregation than their corresponding monomers or shorter oligomers, more than accountable by an additive effect. For example, 60, 3 and 0.3 mM were needed for 50% inhibition of platelet aggregation by lysine, (lys) 3 and (lys) 5, respectively. A similar pattern was observed for the effect of the oligoamines on the activity of the endogenous platelet lectin. The inhibition of platelet aggregation by spermine is competitive, since the effect of a given dose of spermine decreased with increasing platelet concentration. Neither inhibition of platelet-inducer interaction nor Ca 2+ insufficiency explain the inhibitory effects of the oligoamines.