Mucosa of murine detrusor impairs ß2 -adrenoceptor-mediated relaxation.

AIMS: To investigate the role of the mucosa in (-)-isoprenaline-induced relaxation of mouse detrusor muscle and to characterize the ß-adrenoceptor subtypes involved. METHODS: Isolated intact and mucosa-denuded muscle strips from the urinary bladder of male C57BL6 mice were pre-contracted with KCl (40 mM) and were relaxed with increasing concentrations of the ß-adrenoceptor (ß-AR) agonist (-)-isoprenaline and forskolin in the presence and absence of the subtype-selective ß-AR blockers CGP20712A (ß1 -ARs), ICI118,551 (ß2 -ARs), and L748,337 (ß3 -ARs). RESULTS: Force development in response to KCl was larger in mucosa-denuded than in intact preparations and was almost completely relaxed with increasing concentrations of (-)-isoprenaline. Mucosa-denuded muscles were about 10-fold more sensitive to (-)-isoprenaline than intact muscles. CGP20712A did not affect the concentration-response curves (CRCs) to (-)-isoprenaline, ICI118,551 shifted the CRC further to the right in denuded than in intact strips so that the difference between them was abolished. Combined exposure to ß1 -AR and ß2 -AR blocker yielded the same result. L748,337 did not significantly affect the CRC to (-)-isoprenaline but caused additional blockade to ICI118,551 in the presence of intact mucosa. CONCLUSIONS: The mucosa of mouse detrusor strips impairs KCl-induced force development and reduces the sensitivity to ß-AR-induced relaxation. The relaxing response to (-)-isoprenaline as well as the mucosa effect thereupon are mainly mediated by ß2 -ARs. A minor involvement of ß3 -ARs becomes apparent particularly at high (-)-isoprenaline concentrations.