β-Adrenoceptor-Mediated Relaxation of Carbachol-Pre-Contracted Mouse Detrusor

Abstract

Aims: To study the β-adrenoceptor subtypes involved in the relaxation responses to (-)-isoprenaline in carbachol-precontracted (CCh) mouse detrusor muscle with intact and denuded mucosa. Methods: Isolated muscle strips from the urinary bladder of male C57BL6 mice or β 2 -adrenoceptor knockout mice were pre-contracted with CCh, 1 ? M and relaxed with increasing concentrations of the β-adrenoceptor (β-AR) agonist (-)-isoprenaline and forskolin. For estimating the β-AR subtypes involved, subtype-selective receptor blockers were used, that is, CGP 20712A (β 1 -ARs), ICI 118,551 (β 2 -ARs), and L748,337 (β 3 -ARs). Results: Unlike in KCl-precontracted muscle, the mucosa did not affect the sensitivity of the relaxation response to (-)-isoprenaline in CCh-precontracted murine detrusor strips. Increasing concentrations of (-)-isoprenaline produced a biphasic concentrationrelaxation response without any difference both during the presence and absence of mucosa. The relaxation fraction produced by low (-)-isoprenaline concentrations was mediated by β 2 -AR as evidenced by a shift of the concentrationresponse curve to higher concentrations with ICI 118,551, but not with CGP 20712A and L748,337, and by the absence of this fraction in β 2 -AR-KO mice. The relaxation response with low sensitivity to (-)-isoprenaline was not affected by any of the β-AR subtype-selective blockers and was the only response detected in detrusor strips from β 2-AR-KO mice. Conclusions: In CCh-pre-contracted mouse detrusor, β 2 - ARs are responsible for the relaxation component with high sensitivity to (-)-isoprenaline as indicated by the conversion of a biphasic into a monophasic CRC with ICI 118,551 or by its absence in β 2 -AR KO mice. The mucosa does not impair relaxation under these conditions.