title: Effects of intravenous administration of FR122047 (a selective cyclooxygenase 1 inhibitor) and FR188582 (a selective cyclooxygenase 2 inhibitor) on prostaglandin-E2-induced aqueous flare elevation in pigmented rabbits.
abstract: OBJECTIVE
  Two isoforms of cyclooxygenase (COX-1 and COX-2) exist. To determine in vivo effects of the intravenous administration of FR122047 (a selective COX-1 inhibitor), FR188582 (a selective COX-2 inhibitor), diclofenac sodium or dexamethasone phosphate disodium on prostaglandin-E2 (PGE2)-induced aqueous flare elevation and mRNA levels for COX-1 and COX-2 in pigmented rabbits.
  
  
  METHODS
  To produce aqueous flare elevation in rabbits, PGE2, 25 microg/ml, was applied to the cornea with the use of a glass cylinder. FR122047, FR188582, diclofenac sodium or dexamethasone phosphate disodium was intravenously injected before PGE2 application. Aqueous flare was measured with a laser flare-cell meter. The mRNA levels for COX-1 and COX-2 in the iris-ciliary body were determined by real-time polymerase chain reaction.
  
  
  RESULTS
  FR122047, FR188582 and diclofenac sodium (15 micromol/kg each) injected intravenously 30 min before PGE2 application inhibited 29 +/- 5, 40 +/- 12 and 50 +/- 9% of aqueous flare elevation, respectively. Simultaneous injection of FR122047 (15 micromol/kg) and FR188582 (15 micromol/kg) 30 min before PGE2 application inhibited 61 +/- 8% of flare elevation. Dexamethasone phosphate disodium (15 micromol/kg) injected intravenously 300 min before PGE2 application inhibited 68 +/- 8% of aqueous flare elevation. Less than 3-fold changes in mRNA levels for COX-1 and COX-2 in the iris-ciliary body were noted after PGE2, FR122047, FR188582, diclofenac sodium or dexamethasone phosphate disodium treatment.
  
  
  CONCLUSIONS
  It is possible that enzyme activities of both COX-1 and COX-2 may be involved in the mechanism of PGE2-induced aqueous flare elevation in pigmented rabbits.
authors.affiliation: Department of Ophthalmology, Toyama Medical and Pharmaceutical University, Toyama, Japan. ophthal@ms.toyama-mpu.ac.jp
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Abe
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Hayasaka
authors.forename: Xue-Yun
authors.initials: XY
authors.lastname: Zhang
authors.forename: Seiji
authors.initials: S
authors.lastname: Hayasaka
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism; D018916:Blood-Aqueous Barrier / Q000187:drug effects; D002924:Ciliary Body / Q000201:enzymology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007275:Injections, Intravenous; D007498:Iris / Q000201:enzymology; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000235:genetics; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology*; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*
chemical_list: C430892:3-chloro-5-(4-(methylsulfonyl)phenyl)-1-phenyl-1H-pyrazole; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D010879:Piperazines; D011720:Pyrazoles; D012333:RNA, Messenger; D013844:Thiazoles; C085131:1-((4,5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl)-4-methylpiperazine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone