Effect of elementary proline-containing peptides on functional activity of anticoagulation system and primary homeostasis

Abstract

Elementary proline-containing peptides being added to rat platelet-rich plasma or platelet suspension in concentrations of 10-1-10 -7 mg/ml elicit a considerable antiplatelet effect. Efficiency of inhibition of platelet aggregation increases in the following order: ProGly>Pro-Gly-Pro>Gly-Pro-Gly-Gly. Intravenous injection of these peptides activates blood anticoagulation system in experimental animals. Key Words: platelet aggregation; elementary proline-containing peptidesThere are experimental data on various modulating effects of natural and synthetic peptides on blood coagulation system, in particular on initial hemostasis [1,2,5]. In in vitro experiments some peptides (thymosine-al fragments, thymic peptide fraction, etc.) inhibits platelet aggregation (PA) in plateletrich plasma (PRP) and platelet suspension induced by various aggregants [7,11]. Proline residue attached to RGD peptide enhances its antiplatelet activity [10].Some short proline-containing peptides are degradation products of connective tissue proteins (collagen and elastin). Collagen molecule contains numerous Pro-Gly, Gly-Pro, and Pro-Gly-Pro motifs. It has been shown that Pro-Gly and Gly-Pro dipeptides and Pro-Gly-Pro tripeptides activate neutrophils [ 12,13], possess antiulcer activity, and probably exhibit other reg~ effects. Our previous experiments have demonstrated that Thr-Lys-Pro-Arg (tuftsin), Pro-Gly, and TrpPro inhibit the terminal stage of fibrin formation and enhance lysis of unstable fibrin. Apart from the above effects, intravenously injected Pro-Gly peptide inhibits PA in rats [2]. Native collagen is a well known Department of Human and Animal Physiology, Biological Faculty of M. V. Lomonosov Moscow State University inductor of AT. It can be hypothesized that dipeptides, products of collagen degradation, exhibit antiplatelet effect due to blockade of collagen-binding sites.In the present study we explored the effect of elementary proline-containing peptides on PA in vitro and in vivo.

Changes in hemostatic parameters after intranasal administration of peptide Pro-Gly-Pro

“…Studying the dynamics of hemostatic parameters after intranasal administration of Pro-Gly-Pro showed that the anticoagulant effect of this peptide developed over the first minutes after treatment [2] and persisted for 3 or even 5 h. Hemostatic parameters returned to normal 24 h after administration of the peptide. Peptide-induced changes in the enzymatic and nonenzymatic fibrinolytic systems were most persistent.…”

“…Glyprolines, regulatory proline-containing peptides, modulate several processes in the organism, play a role in inhibition of blood coagulation, normalize impaired cerebral circulation, and stimulate nerve regeneration [1,2,10]. Peptides Pro-Gly-Pro and Pro-Gly produce an antithrombotic effect [7], which is related to antiplatelet, anticoagulant, and fibrinolytic activities.…”

Anticoagulation and Antiplatelet Effects of Semax under Conditions of Acute and Chronic Immobilization Stress

“…Simple proline-containing peptides exhibit anticoagulant, fi brinolytic, and antiplatelet effects in the blood stream, stimulating the function of the blood anticoagulation system [3,6]. On the other hand, many regulatory peptides are characterized by wide spectra of biological activities and among other things are involved in the maintenance of normal homeostasis during stress [1,2].…”