Celecoxib inhibits ureteral contractility and prostanoid release.

Travis J Jerde, Jamie L Calamon-Dixon, Dale E Bjorling, Stephen Y Nakada

Department of Surgery, Division of Urology, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA.

Urology 2005 Jan

filter terms:

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) 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. 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. 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.

Citation

Travis J Jerde, Jamie L Calamon-Dixon, Dale E Bjorling, Stephen Y Nakada. Celecoxib inhibits ureteral contractility and prostanoid release. Urology. 2005 Jan;65(1):185-90