title: In vitro effects of the cyclooxygenase inhibitor indomethacin and of the phospholipase-C inhibitor U-73122 on carbachol-induced contractions of porcine detrusor muscle.
abstract: Prostaglandin synthetase inhibitors belong to one substance class additionally used in the treatment of bladder dysfunctions associated with involuntary bladder contractions. However, the mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) on the detrusor muscle is not clear. In this study, it was examined in vitro whether the NSAID indomethacin exhibited an inhibitory effect on carbachol-induced contractions of the porcine detrusor muscle. Additionally, the inhibitory effect of the phospholipase-C inhibitor U-73122 on carbachol-induced contractions of the porcine detrusor muscle was investigated. Experiments were performed on the muscle strips of the porcine detrusor muscle suspended in a tissue bath. Effects of indomethacin at 10(-6) and 10(-5) M on the maximum carbachol-induced contraction and on the carbachol-response curve were investigated. Additionally, the inhibitory influence of U-73122 at a concentration of 10(-5.5) M on the carbachol-response curve was investigated. Pretreatment with indomethacin at both concentrations did not result in a significant reduction in the maximum contraction compared with the control. In the experiments in which carbachol concentration-response curves were generated, indomethacin exhibited at both concentrations a very small but significant change at carbachol concentrations of 10(-8) and 10(-7.5) M. In the experiments with U-73122, a significant change was found in the concentration-response curve of carbachol at all concentrations of carbachol from 10(-6.5) to 10(-4) M. The mean maximum carbachol-induced contraction was 141.8 +/- 6.8% after incubation with U-73122 and 166.0 +/- 6.4% in the control group (P < 0.05). Indomethacin did not inhibit the carbachol-induced contractions of the porcine detrusor muscle. The cyclooxygenase does not play a significant role in the carbachol-induced bladder contraction of the porcine detrusor muscle. The inhibitory action of the phospholipase-C inhibitor U-73122 on the carbachol-induced contraction was significant, but small. The results point to an inferior role of this pathway.
authors.affiliation: Department of Urology, Centre for Surgery, Georg-August-University, Göttingen, Germany. jasmin-katrin.badawi@lycos.de
authors.forename: Jasmin Katrin
authors.initials: JK
authors.lastname: Badawi
authors.forename: Tobias
authors.initials: T
authors.lastname: Seja
authors.forename: Stephan
authors.initials: S
authors.lastname: Bross
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology
chemical_list: D018679:Cholinergic Agonists; D016861:Cyclooxygenase Inhibitors; D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D002217:Carbachol; D010738:Type C Phospholipases; D007213:Indomethacin