Evaluation of arginine-glycine-aspartate-containing peptides as inhibitors of equine platelet function.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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
Publication
Researcher Affiliations
- Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, St Paul 55108, USA.
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.- 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.