Involvement of β3-adrenoceptors in mouse urinary bladder function: Role in detrusor muscle relaxation and micturition reflex

Deba, Aurore; Palea, Stéfano; Rouget, Céline; Westfall, Timothy D.; Lluel, Philippe

doi:10.1016/j.ejphar.2009.07.012

Cited by 21 publications

(29 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CRCs were not affected by tissue exposure to either β1-AR- or β3-AR subtype selective antagonists, suggesting lack of involvement of β 1 -ARs or β 3 -ARs in relaxation of mouse detrusor. Nevertheless, β 3 -AR mediation was claimed using the β 3 -AR-selective agonist CL 316,243, but the relaxant potency of the selective β 3 -AR-agonist is low in mouse [23]. We found a statistically significant shift in the CRCs with the combination of β 1 -AR and β 3 -AR antagonists (see fig.…”

Section: Discussionsupporting

confidence: 50%

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

et al. 2015

View full text Add to dashboard Cite

Aims: To study the β-adrenoceptor subtypes involved in the relaxation responses to (-)-isoprenaline in carbachol-pre-contracted (CCh) mouse detrusor muscle with intact and denuded mucosa. Methods: Isolated muscle strips from the urinary bladder of male C57BL6 mice or β₂-adrenoceptor knockout mice were pre-contracted with CCh, 1 µM 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 (β₁-ARs), ICI 118,551 (β₂-ARs), and L748,337 (β₃-ARs). Results: Unlike in KCl-pre-contracted muscle, the mucosa did not affect the sensitivity of the relaxation response to (-)-isoprenaline in CCh-pre-contracted murine detrusor strips. Increasing concentrations of (-)-isoprenaline produced a biphasic concentration-relaxation response without any difference both during the presence and absence of mucosa. The relaxation fraction produced by low (-)-isoprenaline concentrations was mediated by β₂-AR as evidenced by a shift of the concentration-response curve to higher concentrations with ICI 118,551, but not with CGP 20712A and L748,337, and by the absence of this fraction in β₂-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 β₂-AR-KO mice. Conclusions: In CCh-pre-contracted mouse detrusor, β₂-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 β₂-AR KO mice. The mucosa does not impair relaxation under these conditions.

show abstract

Section: Discussionsupporting

confidence: 50%

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

et al. 2015

View full text Add to dashboard Cite

show abstract

“…These studies have shown roles for both b 2 -and b 3 -AR-mediated effects on the detrusor (Longhurst and Levendusky, 1999;Morita et al, 2000;Michel and Vrydag, 2006), on signaling from the urothelium (Otsuka et al, 2008;Deba et al, 2009;Masunaga et al, 2010;Kullmann et al, 2011), and, latterly, afferent nerve signaling (Kanai et al, 2011;Aizawa et al, 2012). Much of these data have been gathered from in vitro studies or in vivo studies without intact micturition cycles, and as such, the importance of each mechanism in the regulation of the micturition cycle has been difficult to ascertain.…”

Section: Discussionmentioning

confidence: 99%

A Functional Analysis of the Influence of β₃-adrenoceptors on the Rat Micturition Cycle

Sadananda

Drake

Paton³

et al. 2013

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Dysfunctions of the lower urinary tract, such as overactive bladder syndrome and incontinence, are the product of storage failure. Spontaneous regional bladder wall movements [nonmicturition contractions (NMCs)] are proposed to generate afferent activity that signals volume status to the central nervous system. The sympathetic nervous system, via activation of b-adrenoceptors (b-ARs), causes bladder relaxation and promotes urine storage. We hypothesized that b-AR regulation of micturition is mediated by suppression of NMCs. We used an unanesthetized, decerebrate, artificially perfused rat preparation that allows simultaneous cystometry with external urethral sphincter and pelvic afferent nerve recordings. Systemic isoprenaline (10 nM to 1 mM) increased intervoid interval and bladder compliance accompanied by a decrease in NMC amplitude, voiding pressure, and voiding threshold. Isoprenaline also reduced arterial pressure and increased heart rate. The b 3 -AR agonist mirabegron (10-100 nM) increased intervoid interval and bladder compliance and reduced NMC amplitude, yet preserved active voiding function and had no effect on arterial pressure or heart rate. All of these effects of mirabegron were blocked by the selective L748,337), which alone shortened intervoid interval and decreased bladder compliancesuggesting the presence of a basal b 3 -AR-mediated sympathetic tone. Similar effects of mirabegron were seen in an acetic acid-sensitized bladder preparation and in preparations after loss of spinobulbar reflex bladder control. The b 3 -AR-mediated increase in intervoid interval correlated with increased bladder compliance but not with the decrease in NMC amplitude. These findings indicate that b 3 -adrenoceptors have a selective effect that improves urine storage by increasing compliance without affecting the active components of voiding.

show abstract

“…Slow phasic activity could be seen without washing out the CCh. The integral under the tension recording curve could give a simple indication of the amount of phasic activity [12]. Phasic activity was quantified this way for a 3 min period after adding 100 lM CCh, in the presence or absence of IPNA pretreatment.…”

Section: Contractions Induced By Cumulative Addition Of Carbachol (Cch)mentioning

confidence: 99%

β-Adrenoceptor-mediated differences in transverse and longitudinal strips from the rat detrusor

Liang

2010

Int Urol Nephrol

View full text Add to dashboard Cite

Contractions and relaxations of the urinary bladder occur in all directions to facilitate urine release and storage. Transverse and longitudinal contractility of detrusor smooth muscle have been studied before using various pharmacologic stimuli but not β agonists. Given the importance of β-adrenoceptors in mediating bladder relaxation, the effects of isoprenaline (IPNA) in transverse and longitudinal contractility were examined. Pretreatment with a low concentration of IPNA (0.1 or 1 μM) suppressed carbachol (CCh)-induced contractions, more in the transverse than longitudinal direction. Increasing the IPNA concentration to 10 or 100 μM resulted in greater inhibition of longitudinal contractions. Also in the longitudinal direction, IPNA-induced relaxation was greater than in the transverse direction. When precontracted with a submaximal concentration of CCh (1 μM), IPNA increased the phasic activity in the longitudinal direction only. In summary, β-adrenoceptor-mediated differences between transverse and longitudinal contractility were revealed. In testing the relaxant properties of selective β-agonists, the findings here should be considered such that other than the conventional longitudinal contractions, measurements are also made in other directions.

show abstract

Involvement of β3-adrenoceptors in mouse urinary bladder function: Role in detrusor muscle relaxation and micturition reflex

Cited by 21 publications

References 24 publications

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

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

A Functional Analysis of the Influence of β₃-adrenoceptors on the Rat Micturition Cycle

β-Adrenoceptor-mediated differences in transverse and longitudinal strips from the rat detrusor

Contact Info

Product

Resources

About

Involvement of β3-adrenoceptors in mouse urinary bladder function: Role in detrusor muscle relaxation and micturition reflex

Cited by 21 publications

References 24 publications

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

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

A Functional Analysis of the Influence of β3-adrenoceptors on the Rat Micturition Cycle

β-Adrenoceptor-mediated differences in transverse and longitudinal strips from the rat detrusor

Contact Info

Product

Resources

About

A Functional Analysis of the Influence of β₃-adrenoceptors on the Rat Micturition Cycle