RESUMEN
The lipid-lowering, fibrinolytic, and anticoagulant effects of leucine-containing glyprolines, Pro-Gly-Pro-Leu and Leu-Pro-Gly-Pro, were studied in vitro in the blood of patients with disorders of lipid metabolism. The lipid-lowering impact of glyprolines and their ability to reduce the polymerization and to increase the depolymerization of fibrin in human blood were found. Possible mechanisms of lipolytic action of peptides by means of modulation of the lipid-dependent phospholipase A2 were proposed.
Asunto(s)
Hiperlipidemias/tratamiento farmacológico , Metabolismo de los Lípidos/efectos de los fármacos , Oligopéptidos/administración & dosificación , Péptidos/administración & dosificación , Aterosclerosis/sangre , Aterosclerosis/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Humanos , Hiperlipidemias/sangre , Lípidos/sangre , Fosfolipasas A2/sangre , Fosfolipasas A2/efectos de los fármacosRESUMEN
Tetrapeptide Pro-Gly-Pro-Leu in vitro effectively inhibited platelet aggregation over the entire range of studied concentrations (10(-12)-10(-3) M). In concentrations of 10(-9)-10(-3) M it exhibits fibrinolytic activity and in concentrations of 10(-5)-10(-3) M has anticoagulant properties. Under in vivo conditions the analyzed tetrapeptide in a dose of 1 mg/kg increased anticoagulant, total and fibrin depolymerizating activities and increased activity of plasminogen activator. Intravenous administration produced more pronounced anticoagulant effect and leads to a greater increase in activity of plasminogen activator than intranasal administration. Tetrapeptide Pro-Gly-Pro-Leu also exerts antithrombotic effect. Preliminary repeated intranasal administration of the peptide before blood clot formation reduces the weight of fresh fibrin clots.
