Polyamines inhibit both platelet aggregation and glycoprotein IIb/IIIa activation.
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.
Corona-de-la-Peña
Norma
N
Unidad de Investigación Médica en Trombosis, Hemostasia y Aterogénesis, Hospital General Regional Gabriel Mancera, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico. norma_acp@hotmail.com
Uribe-Carvajal
Salvador
S
Barrientos-Rios
Rehotbeverly
R
Matias-Aguilar
Lisnet
L
Montiel-Manzano
Guadalupe
G
Majluf-Cruz
Abraham
A
D015317:Biogenic Polyamines / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D013095:Spermidine / Q000494:pharmacology
D015317:Biogenic Polyamines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013095:Spermidine; D011700:Putrescine