Suburothelial Myofibroblasts in the Human Overactive Bladder and the Effect of Botulinum Neurotoxin Type A Treatment

Roosen, Alexander; Datta, Shubhashis; Chowdhury, Rasheda A.; Patel, Parind; Kalsi, Vinay; Elneil, Sohier; Dasgupta, Prokar; Kessler, Thomas M.; Khan, Shahid; Panicker, Jalesh N.; Fry, Christopher; Brandner, Sebastian; Fowler, Clare J.; Apostolidis, Apostolos

doi:10.1016/j.eururo.2008.11.009

Cited by 74 publications

(60 citation statements)

References 33 publications

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“…Although not a selective ICC marker, vimentin antibodies provide a helpful means of visualizing cell types which may include ICC, within a tissue preparation without labeling SMC. McCloskey and Gurney (2002) later used antibodies to the established ICC marker, c-Kit to demonstrate that the guinea-pig bladder did indeed contain ICC, and this work has since been confirmed by several independent laboratories (Hashitani et al 2004;Biers et al 2006;Shafik et al 2004;Piaseczna Piotrowska et al 2004;Roosen et al 2009). c-Kit is a proto-oncogene that encodes the tyrosine kinase receptor, Kit which is expressed by ICC and mast cells but not SMC or fibroblasts (Maeda et al 1992).…”

Section: Location and Morphology Of Bladder Iccmentioning

confidence: 87%

“…Moreover, Glivec was found to have a marked inhibitory effect on the enhanced spontaneous contractions of whole bladders from spinal cord transected rats, whereas there was little effect on control bladders (Sui et al 2008). Roosen et al (2009) found increased lamina propria connexin 43-immunostaining in human overactive bladder but noted little change in c-Kit expression perhaps indicating that gap junctions numbers were upregulated rather than the actual numbers of ICC. Piaseczna Piotrowska et al (2004) compared the presence of ICC in normal bladders and samples from patients with megacystis-microcolon intestinal hypoperistalsis syndrome and demonstrated marked lack of ICC in the MMIHS sample set.…”

Section: Clinical Significance Of Bladder Iccmentioning

confidence: 87%

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Interstitial Cells of Cajal in the Urinary Tract

McCloskey

2011

Urinary Tract

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The study of novel interstitial cells in the tissues of the urinary tract has defined advances in the field in the last decade. These intriguing cells belong to the same family as the better known interstitial cells of Cajal (ICC) of the gastrointestinal tract, and their discovery has been interpreted to suggest that pacemaker cells may be present in the urinary tract, driving the spontaneous or myogenic activity of the neighboring smooth muscle. This scenario may be true for the urethra where ICC have been described as "loose pacemakers" providing multiple, random inputs to modulate urethral smooth muscle activity. However, there is a paucity of direct evidence available to support this hypothesis in the bladder (where the smooth muscle cells are spontaneously active) or the renal pelvis (where atypical smooth muscle cells are the pacemakers), and it now seems more likely that urinary tract ICC act as modulators of smooth muscle activity.Interestingly, the literature suggests that the role of urinary tract ICC may be more apparent in pathophysiological conditions such as the overactive bladder. Several reports have indicated that the numbers of ICC present in overactive bladder tissues are greater than those from normal tissues; moreover, the contractility of tissues from overactive bladders in vitro appears to be more sensitive to the Kit antagonist, glivec, than those from normal bladder. Future research on urinary tract ICC in the short to medium term is likely to be dynamic and exciting and will lead to increasing our understanding of the roles of these cells in both normal and dysfunctional bladder.

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Section: Location and Morphology Of Bladder Iccmentioning

confidence: 87%

Section: Clinical Significance Of Bladder Iccmentioning

confidence: 87%

Interstitial Cells of Cajal in the Urinary Tract

McCloskey

2011

Urinary Tract

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“…Finally, the increased contractions recorded in the bladders of cats with feline cystitis have been shown to be associated with enhanced calcium transients and supersensitivity to muscarinic stimulation in the urothelium/lamina propria (Ikeda et al, 2009). Thus, it appears possible that spontaneously active cells in the lamina propria may be able to drive detrusor contractions, at least in the overactive bladder where gap junctions are increased (Roosen et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Urothelial/Lamina Propria Spontaneous Activity and the Role of M3 Muscarinic Receptors in Mediating Rate Responses to Stretch and Carbachol

Moro

Uchiyama

Chess-Williams

2011

Urology

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“…In response to physiological stimuli such as mechanical stretch, the urothelium releases transmitters such as ATP and acetylcholine (9,29), and it is proposed that ICs are intermediates in the pathways upon which these transmitters act. The overactive bladder is associated with an increase in IC number in animal and human tissue (12,21); agents that target c-kit receptors on ICs, such as Glivec, reduce spontaneous activity (3), and ICs generate large depolarizing responses to transmitters, such as ATP (28). Excitatory responses from suburothelial ICs to ATP are via P2Y agonists; ADP and UTP generate similar responses to ATP itself (28), and the most readily labeled purinoceptor is the P2Y 6 subtype (26).…”

mentioning

confidence: 99%

Modulation of spontaneous activity in the overactive bladder: the role of P2Y agonists

Fry

Young

Jabr

et al. 2012

American Journal of Physiology-Renal Physiology

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Fry CH, Young JS, Jabr RI, McCarthy C, Ikeda Y, Kanai AJ. Modulation of spontaneous activity in the overactive bladder: the role of P2Y agonists. Am J Physiol Renal Physiol 302: F1447-F1454, 2012. First published February 22, 2012 doi:10.1152/ajprenal.00436.2011Spinal cord transection (SCT) leads to an increase in spontaneous contractile activity in the isolated bladder that is reminiscent of an overactive bladder syndrome in patients with similar damage to the central nervous system. An increase in interstitial cell number in the suburothelial space between the urothelium and detrusor smooth muscle layer occurs in SCT bladders, and these cells elicit excitatory responses to purines and pyrimidines such as ATP, ADP, and UTP. We have investigated the hypothesis that these agents underlie the increase in spontaneous activity. Rats underwent lower thoracic spinal cord transection, and their bladder sheets or strips, with intact mucosa except where specified, were used for experiments. Isometric tension was recorded and propagating Ca 2ϩ and membrane potential (Em) waves were recorded by fluorescence imaging using photodiode arrays. SCT bladders were associated with regular spontaneous contractions (2.9 Ϯ 0.4/min); ADP, UTP, and UDP augmented the amplitude but not their frequency. With strips from such bladders, a P2Y 6-selective agonist (PSB0474) exerted similar effects. Fluorescence imaging of bladder sheets showed that ADP or UTP increased the conduction velocity of Ca 2ϩ /Em waves that were confined to regions of the bladder wall with an intact mucosa. When transverse bladder sections were used, Ca 2ϩ /Em waves originated in the suburothelial space and propagated to the detrusor and urothelium. Analysis of wave propagation showed that the suburothelial space exhibited properties of an electrical syncitium. These experiments are consistent with the hypothesis that P2Y-receptor agonists increase spontaneous contractile activity by augmenting functional activity of the cellular syncitium in the suburothelial space.spinal cord injury; spontaneous contraction; Ca 2ϩ waves; ADP THE OVERACTIVE BLADDER IN patients is associated with spontaneous transient increases in pressure that occur particularly during filling and, if sufficiently severe, contribute to lower urinary tracts symptoms of frequency, urgency, and incontinence (1). The origins of this common pathology are unclear but can be mimicked in animals in which the bladder outflow is artificially obstructed or the spinal cord is transected (SCT; T8 -T9) (12). Whole rat bladders from an SCT model demonstrate large, regular contractions (ϳ2/min) that coincide with waves of raised intracellular Ca 2ϩ and depolarization (E m ) propagating across the surface but originating from one or very few foci. This is in contrast to normal animals where more frequent (5-10/min), low-amplitude contractions are associated with multiple Ca 2ϩ /E m foci (12,14). The detrusor layer of the bladder wall contributes the bulk of tissue and hence most of the Ca 2ϩ /E m signals, but an in...

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Suburothelial Myofibroblasts in the Human Overactive Bladder and the Effect of Botulinum Neurotoxin Type A Treatment

Cited by 74 publications

References 33 publications

Interstitial Cells of Cajal in the Urinary Tract

Interstitial Cells of Cajal in the Urinary Tract

Urothelial/Lamina Propria Spontaneous Activity and the Role of M3 Muscarinic Receptors in Mediating Rate Responses to Stretch and Carbachol

Modulation of spontaneous activity in the overactive bladder: the role of P2Y agonists

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