Celecoxib inhibits ureteral contractility and prostanoid release.
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.
Jerde
Travis J
TJ
Department of Surgery, Division of Urology, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA.
Calamon-Dixon
Jamie L
JL
Bjorling
Dale E
DE
Nakada
Stephen Y
SY
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
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