UNIGE document Scientific Article
previous document  unige:55229  next document
add to browser collection

Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter

Published in Urological Research. 2000, vol. 28, no. 6, p. 376-82
Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are currently considered a first-line treatment of renal colic. Their action has been ascribed to the inhibition of renal prostaglandin synthesis, which decreases renal blood flow and diuresis, and consequently lowers the pressure in the renal pelvis and ureter. However, the effects of NSAIDs on induced contractions of ureteral smooth muscle have received little attention. Also, there is a lack of clinically relevant spasmolytic drugs for the ureter. Therefore, we studied the influence of the non-selective cyclooxygenase (COX) inhibitor diclofenac, a NSAID drug customarily used in the treatment of renal colic, and of NS-398, a selective COX-2 inhibitor, on induced contractions of the pig ureter. Serotonin (0.1-30 microM), norepinephrine (0.1-30 microM) and neurokinin A (0.03-10 microM) induced reproducible concentration-dependent contractions, which were inhibited by diclofenac and NS-398 (10-300 microM) in a concentration-dependent manner. The sensitivity of neurokinin A-induced contractions to diclofenac was 3-4 times greater than that of the amines. Depending on the concentration, inhibition ranged between 25 and 96% of the initially induced contractile activity. In the presence of inhibitors, supramaximal concentrations of agonists were unable to trigger recuperation of the initially induced contractions. Prostaglandin F2alpha did not reverse the effect of diclofenac on agonist-induced contractions. Removal of diclofenac or NS-398 from the organ baths showed that the inhibition was totally reversible. Thus, the non-selective COX inhibitor diclofenac and the selective COX-2 inhibitor NS-398 are almost equipotent in reducing agonist-induced contractions in the isolated porcine ureter. Although the clinical relevance of this spasmolytic effect remains to be demonstrated, the data suggest that patients suffering from renal colic may benefit not only from the anti-diuretic and analgesic effects of diclofenac, but also from its potential spasmolytic properties. Moreover, selective COX-2 inhibitors may have clinical potential, as they may cause fewer side effects.
Keywords AnimalsCyclooxygenase 2Cyclooxygenase 2 InhibitorsCyclooxygenase Inhibitors/pharmacologyDiclofenac/pharmacologyFree Radical Scavengers/pharmacologyIsoenzymes/antagonists & inhibitors/metabolismMuscle Contraction/drug effects/physiologyMuscle, Smooth/physiologyNeurokinin A/pharmacologyNitrobenzenes/pharmacologyNorepinephrine/pharmacologyOrgan Culture TechniquesProstaglandin-Endoperoxide Synthases/metabolismSerotonin/pharmacologySulfonamides/pharmacologySwineSympathomimetics/pharmacologyUreter/drug effects/physiology
PMID: 11221916
Full text
Article (Published version) (150 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Research group Groupe Iselin Christophe (urologie) (106)
(ISO format)
MASTRANGELO, Domenico et al. Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter. In: Urological Research, 2000, vol. 28, n° 6, p. 376-82. doi: 10.1007/s002400000139 https://archive-ouverte.unige.ch/unige:55229

296 hits

0 download


Deposited on : 2015-04-08

Export document
Format :
Citation style :