title: Platelet cyclooxygenase expression in normal dogs.
abstract: BACKGROUND
  Human platelets express both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Variation in COX-2 expression could be a mechanism for variable response to aspirin.
  
  
  OBJECTIVE
  The hypotheses were that circulating canine platelets express COX-1 and COX-2, and that aspirin alters COX expression. The objective was to identify changes in platelet COX expression and in platelet function caused by aspirin administration to dogs.
  
  
  METHODS
  Eight female, intact hounds.
  
  
  METHODS
  A single population, repeated measures design was used to evaluate platelet COX-1 and COX-2 expression by flow cytometry before and after aspirin (10 mg/kg Q12h for 10 days). Platelet function was analyzed via PFA-100(®) (collagen/epinephrine), and urine 11-dehydro-thromboxane B(2) (11-dTXB(2)) was measured and normalized to urinary creatinine. Differences in COX expression, PFA-100(®) closure times, and urine 11-dTXB(2 ): creatinine ratio were analyzed before and after aspirin administration.
  
  
  RESULTS
  Both COX-1 and COX-2 were expressed in canine platelets. COX-1 mean fluorescent intensity (MFI) increased in all dogs, by 250% (range 63-476%), while COX-2 expression did not change significantly (P = 0.124) after aspirin exposure, with large interindividual variation. PFA-100(®) closure times were prolonged and urine 11-dTXB(2) concentration decreased in all dogs after aspirin administration.
  
  
  CONCLUSIONS
  Canine platelets express both COX isoforms. After aspirin exposure, COX-1 expression increased despite impairment of platelet function, while COX-2 expression varied markedly among dogs. Variability in platelet COX-2 expression should be explored as a potential mechanism for, or marker of, variable aspirin responsiveness.
authors: Department of Clinical Sciences, Mississippi State University, Mississippi State, MS 39762-6100, USA. thomason@cvm.msstate.edu
authors: J
authors: J
authors: Thomason
authors: K
authors: K
authors: Lunsford
authors: K
authors: K
authors: Mullins
authors: J
authors: J
authors: Stokes
authors: L
authors: L
authors: Pinchuk
authors: R
authors: R
authors: Wills
authors: R
authors: R
authors: McLaughlin
authors: C
authors: C
authors: Langston
authors: S
authors: S
authors: Pruett
authors: A
authors: A
authors: Mackin
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D051545:Cyclooxygenase 1 / Q000096:biosynthesis / Q000097:blood; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs / Q000097:blood* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000662:veterinary; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000097:blood*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
chemical_list: D016861:Cyclooxygenase Inhibitors; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D003404:Creatinine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin