Mucosa of murine detrusor impairs β2-adrenoceptor-mediated relaxation

Autor: Ursula Ravens, Manja Newe, Stefan Propping, Alberto J. Kaumann, Manfred P. Wirth
Rok vydání: 2014
Předmět:
Zdroj: Neurourology and Urodynamics. 34:592-597
ISSN: 0733-2467
DOI: 10.1002/nau.22627
Popis: Aims To investigate the role of the mucosa in (−)-isoprenaline-induced relaxation of mouse detrusor muscle and to characterize the β-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 β-adrenoceptor (β-AR) agonist (−)-isoprenaline and forskolin in the presence and absence of the subtype-selective β-AR blockers CGP20712A (β1-ARs), ICI118,551 (β2-ARs), and L748,337 (β3-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 β1-AR and β2-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 β-AR-induced relaxation. The relaxing response to (−)-isoprenaline as well as the mucosa effect thereupon are mainly mediated by β2-ARs. A minor involvement of β3-ARs becomes apparent particularly at high (−)-isoprenaline concentrations. Neurourol. Urodynam. 34:592–597, 2015. © 2014 Wiley Periodicals, Inc.
Databáze: OpenAIRE
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