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Evaluation of arginine-glycine-aspartate-containing peptides as inhibitors of equine platelet function.

Abstract: To determine whether synthetic peptides containing the arginine-glycine-aspartate (RGD) sequence inhibit equine platelet function. Methods: For in vitro studies of blood, 3 healthy Thoroughbreds; for in vivo and ex vivo studies of administration of RGD-containing peptides, 4 young adult pony mares. Methods: Blood was incubated with and without addition of aspirin or RGD-containing peptides (RGDS, RPR 110885) and platelet aggregation responses and platelet adhesion to subendothelial collagen were determined. RPR 110885 was administered IV, and platelet function was evaluated. Platelet aggregation was determined by a turbidimetric method, and platelet adhesion was evaluated by the Baumgartner perfusion method. RPR 110885 was administered IV at dosages of 30 and 60 micrograms/kg of body weight, and bleeding time, platelet aggregation responses, and platelet count were determined at hourly intervals for 4 hours. Results: Both RGDS and RPR 110885 inhibited platelet aggregation in vitro in dose-dependent manner and inhibited platelet adhesion to subendothelial collagen. The concentration of RGDS that inhibited platelet aggregation by 50% (IC50) was 100 to 142 microM for the various agonists tested, whereas the concentration of RPR 110885 that inhibited platelet aggregation by 50% was 0.03 to 0.05 microM. When administered to ponies at 30 or 60 g/kg, RPR 110885 almost completely inhibited ADP-induced platelet aggregation. Conclusions: RGDS and RPR 110885 inhibited equine platelet function; however, RPR 110885 was several thousand times more potent than RGDS. Conclusions: RGD-containing peptides may be useful for treatment of thrombotic diseases of horses.
Publication Date: 1997-05-01 PubMed ID: 9140550
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article discusses an experiment conducted in horses to assess whether synthetic peptides, specifically those that contain the arginine-glycine-aspartate (RGD) sequence, can inhibit platelet function. The study found that these peptides, indeed, inhibited equine platelet aggregation and adhesion—an observation that suggests a potential use of these peptides in the treatment of thrombotic diseases in horses.

Research Objective

The aim of this study was to determine whether synthetic peptides containing the arginine-glycine-aspartate (RGD) sequence have an inhibitory effect on equine platelet function. Two peptides—a simple RGD-containing peptide (RGDS) and a more complex one (RPR 110885)—were tested both in vitro and in vivo.

Methods

  • Blood samples for in vitro studies were obtained from three healthy Thoroughbreds, while in vivo and ex vivo evaluations involved four young adult pony mares.
  • The synthetic peptides were added to the blood samples and the responses were compared to those involving aspirin—a known platelet function inhibitor.
  • The platelet aggregation responses were determined by a turbidimetric method, a technique measuring cloudiness of a solution, and platelet adhesion to collagen was evaluated by the Baumgartner perfusion method.
  • The RPR 110885 was administered intravenously at dosages of 30 and 60 micrograms/kg of body weight. The bleeding time, platelet aggregation responses, and platelet count were then determined at hourly intervals for 4 hours.

Results

  • Both RGDS and RPR 110885 significantly inhibited platelet aggregation and adhesion in a dose-dependent manner.
  • The concentration of RGDS required to inhibit 50% of platelet function was 100-142 microM; for RPR 110885, only 0.03–0.05 microM was needed.
  • When RPR 110885 was administered to ponies in doses as low as 30 or 60 g/kg, it almost entirely halted ADP-induced platelet aggregation.

Conclusions

  • The study showed that both RGDS and RPR 110885 inhibit equine platelet function. However, RPR 110885 has a potency several thousand times greater than RGDS.
  • Synthetic peptides containing the RGD sequence may have potential use in the treatment of thrombotic disorders in horses.

Cite This Article

APA
Weiss DJ, Evanson OA, Wells RE. (1997). Evaluation of arginine-glycine-aspartate-containing peptides as inhibitors of equine platelet function. Am J Vet Res, 58(5), 457-460.

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 58
Issue: 5
Pages: 457-460

Researcher Affiliations

Weiss, D J
  • Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, St Paul 55108, USA.
Evanson, O A
    Wells, R E

      MeSH Terms

      • Animals
      • Arginine / analysis
      • Aspartic Acid / analysis
      • Aspirin / pharmacology
      • Blood Coagulation / drug effects
      • Blood Coagulation / physiology
      • Blood Platelets / drug effects
      • Blood Platelets / physiology
      • Dose-Response Relationship, Drug
      • Fibrinogen / metabolism
      • Glycine / analysis
      • Horses / blood
      • Horses / physiology
      • Oligopeptides / chemistry
      • Oligopeptides / pharmacology
      • Platelet Adhesiveness / drug effects
      • Platelet Adhesiveness / physiology
      • Platelet Aggregation / drug effects
      • Platelet Aggregation / physiology
      • Platelet Aggregation Inhibitors / pharmacology
      • Platelet Count
      • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors

      Citations

      This article has been cited 1 times.
      1. Wu X, Mogford JE, Platts SH, Davis GE, Meininger GA, Davis MJ. Modulation of calcium current in arteriolar smooth muscle by alphav beta3 and alpha5 beta1 integrin ligands. J Cell Biol 1998 Oct 5;143(1):241-52.
        doi: 10.1083/jcb.143.1.241pubmed: 9763435google scholar: lookup