Polyamines Inhibit Both Platelet Aggregation and Glycoprotein IIb/IIIa Activation

Abstract

Platelet aggregation is inhibited by the polyamines putrescine, spermidine, and spermine. To date, the mechanism of action has not been clearly identified. Evidence suggests that polyamines may interact with the fibrinogen receptor (GP IIb/IIIa), interfering with platelet-platelet attachment. The effect of polyamines on human platelet aggregation and GP IIb/IIIa activation was evaluated. For the aggregation experiments, platelets were obtained from heparin- or citrate-collected blood. Our results indicate that the polyamines putrescine, spermidine, and spermine cause a dose-dependent inhibition of ADP- or collagen-mediated platelet aggregation with an order of potency spermine>spermidine>putrescine. In addition, spermine arrests or inhibits thrombin-, epinephrine-, arachidonate-, or ristocetin-induced platelet aggregation. Expression of platelet membrane glycoproteins IIb, IIIa, and IX is not reduced by polyamines. However, spermine inhibits the ADP- or thrombin-induced activation of GP IIb/IIIa. It is concluded that the final step in aggregation, common to all agonists, ie, fibrinogen binding to GP IIb/IIIa, is inhibited by spermine through inhibition of the agonist-induced activation of GP IIb/IIIa that precedes fibrinogen-ligand binding.

The effects of polyamines on human colonic mucosal function

“…The results also demonstrate that polyamines exert no physiologically significant difference on basal electrogenic secretion than controls. Many of the physiological properties of polyamines appear to be linked with their valency -this was shown in the results of the Ussing chamber studies as well as cAMP quantification, and parallels with findings from other functional studies (Cheng et al, 2004;Corona-de-la-Pena et al, 2005).…”

Modulation of the Cationic Amino Acid Transport System y⁺L by Surface Potential, Ouabain and Thrombin in Human Platelets: Effects of Uremia

“…Since polyamines have been reported to inhibit platelet aggregation [30], we examined whether polyamines modulate system y + L activity. Following incubation of platelet suspensions with increasing concentrations of putrescine (2–10 µ M ), L -arginine influx (1 µ M ) was unchanged (n = 5) (data not shown).…”

Inhibition of polyphosphate as a novel strategy for preventing thrombosis and inflammation

“…30 Our finding that spermine, norspermine, and spermidine are potent polyP inhibitors is noteworthy because the naturally occurring polyamines, spermine, spermidine, and putrescine inhibit aggregation of human platelets, [31][32][33][34][35][36][37] and systemic administration of polyamines is reported to prevent carotid artery occlusion in a canine thrombosis model. 38 The latter investigators concluded that the antithrombotic activity of polyamines was the result of inhibition of platelet aggregation, although it is tempting to speculate that inhibition of platelet-secreted polyP procoagulant activity may have also contributed to their protective effects.…”