Mucosa of murine detrusor impairs β₂-adrenoceptor-mediated relaxation

Abstract

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.

β-Adrenoceptor-mediated Relaxation of Urinary Bladder Muscle in β2-Adrenoceptor Knockout Mice

“…These findings confirm our previous observations ( Wuest et al, 2009 ; Propping et al, 2013 , 2015a ) that β 2 -ARs are the major β-AR subtype mediating relaxation in WT detrusor strips. However, given the low affinity of L748,337 for murine β 3 -ARs ( Cernecka et al, 2014 ), the concentration of 100 nM L748,337 may not have been sufficient to block murine β 3 -AR.…”

“…Subtypes involved in mouse bladder are controversial. While we have found that detrusor relaxation is mediated via β 2 -AR ( Wuest et al, 2009 ; Propping et al, 2015a ), other authors have suggested β 3 -ARs as the relevant subtype ( Deba et al, 2009 ). Some of this discrepancy may be due to different experimental conditions, but another major issue is that the various drugs employed may actually not exhibit the assumed β-AR subtype selectivity ( Cernecka et al, 2014 ).…”

“…Characterization of mice: the WT and β 2 -AR KO mice had average body weights of 29 ± 3 g for WT ( n = 55) and 28 ± 4 g for β 2 -AR KO mice ( n = 49). Strips of mouse urinary bladder were dissected as described previously ( Propping et al, 2015a , b ). Muscle strips with an intact mucosal layer (mean weight WT mice 2.9 ± 1.6 mg, n = 75 strips; β 2 -AR KO mice 2.4 ± 1.8 mg, n = 74, P = 0.26) were mounted in an organ bath filled with 5 ml of modified Tyrode solution of the following composition (in mM): NaCl 126.9, KCl 5.4, MgCl 2 1.05, CaCl 2 1.8, NaH 2 HPO 4 0.45, NaHCO 3 22, EDTA 0.04, ascorbic acid 0.2, glucose 5.6.…”

“…All β-AR subtype-selective blockers were added 30 min before the start of KCl pre-contraction and remained in the bath solution throughout the remainder of the experiment. The concentrations of antagonists were CGP 20712A 300 nM, ICI 118,551 50 nM ( Wuest et al, 2009 ; Propping et al, 2015a ), and L748,337 100 nM to 10 μM ( Deba et al, 2009 ).…”

Effects of β‐adrenoceptor activation on haemodynamics during hypoxic stress in rats

“…We used atenolol (Bogaert, Rosseel, & Lefebvre, 1984;Prachi, Komal, & Priti, 2017), ICI 118,551 (Baker, 2010;Propping, Newe, Kaumann, Wirth, & Ravens, 2015) and propranolol (Hoffmann, Leitz, Oberdorf-Maass, Lohse, & Klotz, 2004;Tan & Yang, 2016;Zhang et al, 2011b) as the selective β 1 -AR, selective β 2 -AR and non-selective β-AR antagonists, respectively. The doses of the β-AR antagonists were selected according to our previous experimental data, which were shown to be the optimal doses for stable monitoring of haemodynamics (Zhang et al, 2011a(Zhang et al, , 2012.…”