Comparison study of autonomous activity in bladders from normal and paraplegic rats

Gevaert, Thomas; Ost, Dieter; Ridder, Dirk De

doi:10.1002/nau.20206

Cited by 19 publications

(17 citation statements)

References 29 publications

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“…13 In decentralised rat bladders, an enhanced and direct contractile role for M2 has been reported. 14 Similar results were reported in obstructed 15 and neurogenic 16,17 rat bladders. In humans, such altered M2 function might also develop in neurogenic detrusor overactivity, although there are conflicting reports on this topic.…”

Section: Discussionsupporting

confidence: 83%

199 Role of M2 and M3 Muscarinic Acetylcholine Receptor Subtypes in Activation of Bladder Afferent Pathways in Spinal Cord Injured Rats

Matsumoto¹,

Kita²,

Miyazato³

et al. 2010

Journal of Urology

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Purpose-In this study, we evaluated the role of M2 and M3 mAChR subtypes in activation of bladder afferent pathways in rats with chronic spinal cord injury (SCI).Materials and Methods-Adult female Sprague-Dawley rats were spinalized at the Th9 level. Continuous cystometry was performed under an awake condition 2 or 4 weeks after SCI. The effects of intravesical administration of an mAChR agonist (oxotremorine-M; Oxo-M), a nonselective antagonist (atropine), an M2-selective antagonist (methoctramine) and an M3-selective antagonist (darifenacin) were examined. After cystometry, the bladder was removed and separated into mucosa and detrusor, and M2 and M3 mAChR mRNA expression in the mucosa was determined with real time quantitative PCR.Results-At 2 and 4 weeks after SCI, intravesical administration of a non-selective mAChR agonist (25μM Oxo-M) increased the area under the curve of non-voiding contractions (NVCs) although intercontraction interval (ICI) of voiding contractions and maximum voiding pressure (MVP) did not change. This effect was blocked by atropine and methoctramine (10μM), but not by darifenacin (50μM). However, mAChR antagonists alone (50μM) had no effect on cystometric parameters. M2 mAChR mRNA expression was increased in mucosa of SCI rats compared to normal rats.Conclusions-Our results suggest that the M2 mAChR subtype plays an important role in bladder afferent activation that enhances detrusor overactivity in SCI rats. However, because mAChR antagonists alone did not affect any cystometric parameters, the muscarinic mechanism controlling bladder afferent activity may not be involved in the emergence of detrusor overactivity in SCI.

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Section: Discussionsupporting

confidence: 83%

199 Role of M2 and M3 Muscarinic Acetylcholine Receptor Subtypes in Activation of Bladder Afferent Pathways in Spinal Cord Injured Rats

Matsumoto¹,

Kita²,

Miyazato³

et al. 2010

Journal of Urology

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“…M 2 receptors have been shown to play an indirect role in detrusor contraction by inhibiting bladder smooth muscle relaxation and enhancing detrusor contraction via G i inhibition of cAMP levels [Ehlert et al, 2005]. In pathologic states, the M 2 receptor pathway has a greater role in mediating contraction in rats and humans [Braverman and Ruggieri, 2003;Pontari et al, 2004;Gevaert et al, 2006]. Thus, with pathophysiological stressors, the mechanisms that transduce the muscarinic contractile signal can become altered such that the M 2 receptor subtype plays a more prominent role in the contractile response that is normally mediated by the M 3 receptor subtype.…”

Section: Introductionmentioning

confidence: 99%

M₂ mediated contractions of human bladder from organ donors is associated with an increase in urothelial muscarinic receptors

Braverman¹,

Лебед²,

Linder³

et al. 2006

Neurourology and Urodynamics

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Aims: Previous studies have shown increased density of M 2 receptors in hypertrophied rat bladders that possess an M 2 contractile phenotype. The aim of the current study is to determine whether human bladders with an M 2 contractile phenotype also have a greater density of bladder M 2 receptors. Materials and Methods: Human bladders were obtained from 24 di¡erent organ transplant donors. Darifenacin and methoctramine a⁄nity was determined by the rightward shift of cumulative carbachol concentration contractile response curves for each bladder. Radioligand binding and immunoprecipitation was used to quantify M 2 and M 3 subtypes in isolated detrusor muscle and urothelium. In addition, pig bladder muscle and urothelial receptors were quanti¢ed for comparison. Results: In the human urothelium total, M 2 and M 3 muscarinic receptor density is signi¢cantly negatively correlated with the a⁄nity of darifenacin for inhibition of contraction of the detrusor muscle. In the detrusor muscle there is no correlation between receptor density and darifenacin a⁄nity for inhibition of contraction. Muscarinic receptor density is greater in the muscle than in the urothelium in human bladders whereas in the pig bladder the density is greater in the urothelium than in the muscle. Conclusions: The greater density of urothelial muscarinic receptors in human bladders with lower darifenacin a⁄nity, indicative of a greater contribution of M 2 receptors to the contractile response, points towards a possible role of the urothelium in controlling M 2 mediated contractile phenotype. In comparison between human and pig bladders, the distribution of muscarinic receptor subtypes in the muscle and urothelium are quite di¡erent.

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“…SIC were defined using the analytic criteria as used before in whole bladders experiments. 15 Briefly, SIC are defined as tension changes of at least 0.500 mN, lasting between 3 and 10 sec and ending when the tension level had fallen to 25% of its original height. Frequency of SIC was calculated by counting SIC per 120 sec.…”

Section: Muscle Strip Experimentsmentioning

confidence: 99%

Maturation of stretch‐induced contractile activity and its muscarinic regulation in isolated whole bladder strips from rat

Gevaert

Owsianik

Hutchings

et al. 2010

Neurourology and Urodynamics

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Comparison study of autonomous activity in bladders from normal and paraplegic rats

Cited by 19 publications

References 29 publications

199 Role of M2 and M3 Muscarinic Acetylcholine Receptor Subtypes in Activation of Bladder Afferent Pathways in Spinal Cord Injured Rats

199 Role of M2 and M3 Muscarinic Acetylcholine Receptor Subtypes in Activation of Bladder Afferent Pathways in Spinal Cord Injured Rats

M₂ mediated contractions of human bladder from organ donors is associated with an increase in urothelial muscarinic receptors

Maturation of stretch‐induced contractile activity and its muscarinic regulation in isolated whole bladder strips from rat

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Comparison study of autonomous activity in bladders from normal and paraplegic rats

Cited by 19 publications

References 29 publications

199 Role of M2 and M3 Muscarinic Acetylcholine Receptor Subtypes in Activation of Bladder Afferent Pathways in Spinal Cord Injured Rats

199 Role of M2 and M3 Muscarinic Acetylcholine Receptor Subtypes in Activation of Bladder Afferent Pathways in Spinal Cord Injured Rats

M2 mediated contractions of human bladder from organ donors is associated with an increase in urothelial muscarinic receptors

Maturation of stretch‐induced contractile activity and its muscarinic regulation in isolated whole bladder strips from rat

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M₂ mediated contractions of human bladder from organ donors is associated with an increase in urothelial muscarinic receptors