Synergistic inhibition of platelet aggregation by fibrinogen-related peptides.
We have evaluated the ability of the fibrinogen-related peptides Gly-Arg-Gly-Asp-Ser (GRGDS), Gly-Gln-Gln-His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val (gamma-chain peptide), and Gly-Pro-Arg-Pro (GPRP) to inhibit platelet aggregation in platelet-rich plasma individually and in combination. When used alone, GRGDS totally inhibited ADP-induced aggregation of human platelets in platelet-rich plasma; however, the maximum inhibitory effect of the other peptides was less than 80%. The concentrations necessary to inhibit platelet aggregation in plasma by 50% were 100 mumols/l and 1 and 3.2 mmol/l for GRGDS, gamma-chain peptide, and GPRP, respectively. When evaluating the effect of peptide mixtures, we discovered that the combination GPRP + GRGDS worked together synergistically (p less than 0.001, analysis by surface response methodology), whereas GPRP + gamma-chain peptide did not. For example, our analysis indicated that a mixture of 50 mumols/l GRGDS plus 180 mumols/l GPRP would produce 50% inhibition of platelet aggregation. This is an effect twofold greater than that produced by 50 mumols/l GRGDS alone, and one that would require an 18-fold greater concentration of GPRP if used alone. These data indicate that the combination GPRP + GRGDS inhibited platelet aggregation in plasma in a synergistic fashion and suggest the potential value of their combined use in antithrombotic therapy.
Department of Medicine, Medical College of Virginia, Richmond, VA.
B
B
Adelman
C
C
Gennings
J
J
Strony
E
E
Hanners
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D004357:Drug Synergism; D005340:Fibrinogen / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; C034585:glycyl-prolyl-arginyl-proline; D005340:Fibrinogen; C049554:glycyl-arginyl-glycyl-aspartyl-serine