title: Celecoxib inhibits ureteral contractility and prostanoid release.
abstract: OBJECTIVE
  To evaluate the efficacy and potency of clinically available celecoxib for inhibition of ureteral contractility and prostanoid release. We have previously reported that the selective cyclooxygenase (COX)-2 inhibitor NS-398 inhibits ureteral contractility.
  
  
  METHODS
  We evaluated the release of prostaglandin (PG) E2, F2alpha, D2, thromboxane B2 (a thromboxane2 metabolite), and 6-keto-PGF1alpha (a prostacyclin metabolite) by gas chromatography-mass spectrometry from porcine ureters in the presence and absence of tumor necrosis factor-alpha (TNF-alpha), a putative cyclooxygenase (COX)-2 inducer. PGE2 and PGF2alpha were the prostanoids released in greatest quantity in response to TNF-alpha. We subsequently measured spontaneous contractility and prostanoid release in porcine ureters treated with 0.1, 1.0, or 10 microM concentrations of indomethacin (nonselective COX inhibitor), NS-398, celecoxib, or 0.1% dimethyl sulfoxide (vehicle) for 2 hours. Ureteral contractility and prostanoid release were measured every 15 minutes after the addition of the various compounds. We also treated ureters with 10 ng/mL TNF-alpha and all three COX inhibitors or dimethyl sulfoxide for 2 and 4 hours and measured the PGE2 and PGF2alpha release.
  
  
  RESULTS
  Celecoxib, indomethacin, and NS-398 inhibited ureteral contractility and prostanoid release with similar efficacy and potency. All three compounds also reduced TNF-alpha-induced prostanoid release to control levels at concentrations as low as 0.1 microM.
  
  
  CONCLUSIONS
  Our data have indicated that celecoxib and indomethacin inhibit PG release by the ureter to a similar degree, even in the presence of COX-2 induction. Animal experiments and clinical trials evaluating the safety and efficacy of celecoxib for the treatment of symptomatic ureteral obstruction are warranted.
authors.affiliation: Department of Surgery, Division of Urology, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Jerde
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Calamon-Dixon
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bjorling
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Nakada
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D003864:Depression, Chemical; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009578:Nitrobenzenes / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011720:Pyrazoles / Q000009:adverse effects / Q000494:pharmacology*; D012636:Secretory Rate / Q000187:drug effects; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology*; D034421:Sus scrofa; D013928:Thromboxane A2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014513:Ureter / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014517:Ureteral Obstruction / Q000188:drug therapy
chemical_list: D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D000068579:Celecoxib; D015232:Dinoprostone; D015230:Prostaglandin D2; D007213:Indomethacin; D004121:Dimethyl Sulfoxide