Effects of a non-selective COX inhibitor and selective COX-2 inhibitors on contractility of human and porcine ureters in vitro and in vivo

Chaignat, Valérie; Danuser, Hansjörg; Stoffel, Michael Hubert; Z'Brun, Sebastian; Studer, U E; Mevissen, Meike (2008). Effects of a non-selective COX inhibitor and selective COX-2 inhibitors on contractility of human and porcine ureters in vitro and in vivo. British journal of pharmacology, 154(6), pp. 1297-307. Oxford: Wiley-Blackwell 10.1038/bjp.2008.193

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BACKGROUND AND PURPOSE: Anti-inflammatory drugs are used in the treatment of acute renal colic. The aim of this study was to investigate the effects of selective COX-2 inhibitors and the non-selective COX inhibitor diclofenac on contractility of human and porcine ureters in vitro and in vivo, respectively. COX-1 and COX-2 receptors were identified in human ureter and kidney. EXPERIMENTAL APPROACH: Human ureter samples were used alongside an in vivo pig model with or without partial ureteral obstruction. COX-1 and COX-2 receptors were located in human ureters by immunohistochemistry. KEY RESULTS: Diclofenac and valdecoxib significantly decreased the amplitude of electrically-stimulated contractions in human ureters in vitro, the maximal effect (Vmax) being 120 and 14%, respectively. Valdecoxib was more potent in proximal specimens of human ureter (EC50=7.3 x 10(-11) M) than in distal specimens (EC50=7.4 x 10(-10) M), and the Vmax was more marked in distal specimens (22.5%) than in proximal specimens (8.0%) in vitro. In the in vivo pig model, parecoxib, when compared to the effect of its solvent, significantly decreased the maximal amplitude of contractions (Amax) in non-obstructed ureters but not in obstructed ureters. Diclofenac had no effect on spontaneous contractions of porcine ureter in vivo. COX-1 and COX-2 receptors were found to be expressed in proximal and distal human ureter and in tubulus epithelia of the kidney. CONCLUSIONS AND IMPLICATIONS: Selective COX-2 inhibitors decrease the contractility of non-obstructed, but not obstructed, ureters of the pig in vivo, but have a minimal effect on electrically-induced contractions of human ureters in vitro.

Item Type:	Journal Article (Original Article)
Division/Institute:	05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Anatomy 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology 05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Pharmacology and Toxicology
UniBE Contributor:	Chaignat, Valérie, Danuser, Hansjörg, Stoffel, Michael Hubert, Z'Brun, Sebastian, Studer, Urs, Mevissen, Meike
Subjects:	500 Science > 570 Life sciences; biology 600 Technology > 630 Agriculture 600 Technology > 610 Medicine & health
ISSN:	0007-1188
Publisher:	Wiley-Blackwell
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:04
Last Modified:	05 Dec 2022 14:19
Publisher DOI:	10.1038/bjp.2008.193
PubMed ID:	18500363
Web of Science ID:	000257613300014
URI:	https://boris.unibe.ch/id/eprint/27986 (FactScience: 115397)