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. We evaluated the release of prostaglandin (PG) E 2, F2α, D2, thromboxane B2 (a thromboxane2 metabolite), and 6-keto-PGF1α (a prostacyclin metabolite) by gas chromatography-mass spectrometry from porcine ureters in the presence and absence of tumor necrosis factor-alpha (TNF-α), a putative cyclooxygenase (COX)-2 inducer. PGE2 and PGF2α were the prostanoids released in greatest quantity in response to TNF-α. We subsequently measured spontaneous contractility and prostanoid release in porcine ureters treated with 0.1, 1.0, or 10 μM 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-α and all three COX inhibitors or dimethyl sulfoxide for 2 and 4 hours and measured the PGE2 and PGF2α release. Celecoxib, indomethacin, and NS-398 inhibited ureteral contractility and prostanoid release with similar efficacy and potency. All three compounds also reduced TNF-α-induced prostanoid release to control levels at concentrations as low as 0.1 μM. 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.
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