title: Evaluation of arginine-glycine-aspartate-containing peptides as inhibitors of equine platelet function.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, St Paul 55108, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Weiss
authors.forename: O A
authors.initials: OA
authors.lastname: Evanson
authors.forename: R E
authors.initials: RE
authors.lastname: Wells
mesh_terms: D000818:Animals; D001120:Arginine / Q000032:analysis; D001224:Aspartic Acid / Q000032:analysis; D001241:Aspirin / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000378:metabolism; D005998:Glycine / Q000032:analysis; D006736:Horses / Q000097:blood* / Q000502:physiology; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors
chemical_list: D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D001224:Aspartic Acid; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen; D001120:Arginine; C046617:arginyl-glycyl-aspartyl-serine; D001241:Aspirin; D005998:Glycine