Inhibition of Human Detrusor Contraction by a Urothelium Derived Factor

Chaiyaprasithi, B.; Mang, Christian; Kilbinger, H.; Hohenfellner, Markus

doi:10.1097/01.ju.0000091870.51841.ae

Cited by 77 publications

(91 citation statements)

References 9 publications

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“…1c). These results are in line with the existence of an ‘urothelium-derived relaxing factor [3,4,5,7]. Tension decline of CCh-induced contraction in a similar time window as required for the (-)-isoprenaline application (time-matched controls, TMC) was 13 ± 2% in intact and 14 ± 4% in denuded strips.…”

Section: Resultssupporting

confidence: 73%

“…We have shown previously, that the presence of the mucosa attenuates the contractile response to KCl supporting the existence of an urothelium-derived relaxing factor [3,4]; however, others could not demonstrate this effect [5]. Our study also provided evidence that the mucosa may impair relaxation in response to (-)-isoprenaline.…”

Section: Discussionsupporting

confidence: 66%

“…Maximum KCl-stimulated contractions of human and murine muscle strips are lower in intact strips than when the urothelium has been removed [3,4], although some groups did not find any difference [5]. In several species, contractions elicited via muscarinic receptor stimulation are also smaller in intact than denuded detrusor strips [4,5,6,7,8,9,10,11], suggesting that the urothelium exerts a relaxing effect on bladder muscle, which is assumed to be mediated by an unknown diffusible factor. The specific characteristic of this ‘urothelium-derived relaxing factor' has not been determined [5,7].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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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.

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Section: Resultssupporting

confidence: 73%

Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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“…Conflicting results were reported for contractions elicited by KCl depolarization, the urothelium having been associated with either a robust effect [7] or no effect at all [9]. In particular, the differences between denuded and intact detrusor strips faded during steady-state force development [6].…”

Section: Introductionmentioning

confidence: 80%

“…In ex vivo experiments, the mucosa of the human urinary bladder provides significant inhibitory effects on detrusor contractions in response to various modes of stimulation, for example, muscarinic agonists [3,4,5,6,7], tachykinins [8] or electric field stimulation [9,10]. Conflicting results were reported for contractions elicited by KCl depolarization, the urothelium having been associated with either a robust effect [7] or no effect at all [9].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Modulation of Mucosa-Related Impairment of β-Adrenoceptor-Mediated Relaxation in Human Detrusor

et al. 2015

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Objectives: The mucosa of human detrusor strips impairs catecholamine-induced relaxation. In order to elucidate which signal transduction pathways are involved in this cross talk between the mucosa and detrusor, we have studied the effects of several pharmacological agonists and antagonists on noradrenaline-mediated relaxation in intact and mucosa-denuded detrusor strips. Patients and Methods: Strips of detrusor tissue were obtained from patients who had undergone cystectomy for bladder cancer and were set up for force measurement. KCl- or carbachol-precontracted strips were relaxed with increasing concentrations of noradrenaline in the absence and in the presence of nitric oxide synthase inhibitor, L-NAME; P2X-receptor antagonist, PPADS; ET_A-receptor antagonist, BQ-123; ET_B-receptor antagonist, BQ-788; cyclooxygenase inhibitor, diclofenac; AT₁-receptor antagonist, candesartan; and NK₁-receptor antagonist, L-703,606. Results: In intact strips, KCl-stimulated force was enhanced by all blockers; carbachol-stimulated force increased with L-703,606. In denuded strips, only L-NAME augmented the KCl-stimulated contraction. Noradrenaline relaxed the precontracted detrusor strips to a significantly larger extent and at lower concentrations in denuded than in intact strips. L-NAME, PPADS and BQ-123/BQ-788 had little effect on noradrenaline-induced relaxation, whereas diclofenac, candesartan and L-703,606 sensitized intact carbachol-stimulated detrusor strips to noradrenaline-induced relaxation. Conclusion: Inhibition of the noradrenaline-induced relaxation of precontracted human detrusor strips by the mucosa is attenuated by diclofenac, candesartan and L-703,606 suggesting the involvement of prostanoids, angiotensin and neurokinin pathways. Further experiments are required to unravel the exact mechanisms.

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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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Inhibition of Human Detrusor Contraction by a Urothelium Derived Factor

Abstract: Muscarinic agonists stimulate the release of an inhibitory factor from the human urothelium. The factor is distinct from nitric oxide and it persists in the presence beta-adrenoceptor blockade or cyclooxygenase inhibition.

Cited by 77 publications

References 9 publications

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

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

Pharmacological Modulation of Mucosa-Related Impairment of β-Adrenoceptor-Mediated Relaxation in Human Detrusor

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

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Inhibition of Human Detrusor Contraction by a Urothelium Derived Factor

Abstract: Muscarinic agonists stimulate the release of an inhibitory factor from the human urothelium. The factor is distinct from nitric oxide and it persists in the presence beta-adrenoceptor blockade or cyclooxygenase inhibition.

Cited by 77 publications

References 9 publications

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

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

Pharmacological Modulation of Mucosa-Related Impairment of β-Adrenoceptor-Mediated Relaxation in Human Detrusor

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

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