The molecular basis of urgency: regional difference of vanilloid receptor expression in the human urinary bladder

Liu, Lu; Mansfield, Kylie J; Kristiana, Ika; Vaux, Kenneth J.; Millard, R. J.; Burcher, Elizabeth

doi:10.1002/nau.20326

Cited by 71 publications

(52 citation statements)

References 33 publications

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“…A trend suggesting a similar correlation was found with TRPV1 immunoreactive fibers. Very recently, Liu et al 43 demonstrated that in patients with sensory urgency without DO, TRPV1 mRNA is increased in the trigonal mucosa and correlates with a lower volume associated with first bladder sensation to urinate. Thus, the possibility of inactivating bladder C-fibers by the two neurotoxins seems to be an attractive possibility to treat urgency refractory to antimuscarinic drugs.…”

Section: Results With Rtx and Btx-a In Patients With Urgencymentioning

confidence: 99%

Resiniferatoxin and botulinum toxin type A for treatment of lower urinary tract symptoms

Cruz

Dinis

2007

Neurourol. Urodyn.

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Resiniferatoxin (RTX) and botulinum toxin subtype A (BTX-A) are increasingly viewed as potential treatments for lower urinary tract symptoms (LUTS) refractory to conventional therapy. RTX, a capsaicin analogue devoid of severe pungent properties, acts by desensitizing the transient receptor potential vanilloid type 1 (TRPV1) receptor and inactivating C-fibers. BTX-A cleaves soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in afferent and efferent nerve endings, therefore impeding the fusion of synaptic vesicles with the neuronal membrane necessary for the release of neurotransmitters. In patients with neurogenic and idiopathic detrusor overactivity, RTX and BTX-A have been shown to increase the volume to first detrusor contraction, increase bladder capacity, and improve urinary incontinence and quality of life. Recent data also suggest a role for these neurotoxins in treating urgency, the primary symptom in overactive bladder (OAB) syndrome. Furthermore, experimental data strongly support the use of both neurotoxins in the treatment of pain and frequency in patients with interstitial cystitis/painful bladder syndrome (IC/PBS), although the results from available clinical trials for this use are still inconclusive. In spite of promising results overall, it should be made clear that the administration of these neurotoxins is still considered an experimental procedure and that more clinical studies are necessary before a license for their use will be issued by health authorities.

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Section: Results With Rtx and Btx-a In Patients With Urgencymentioning

confidence: 99%

Resiniferatoxin and botulinum toxin type A for treatment of lower urinary tract symptoms

Cruz

Dinis

2007

Neurourol. Urodyn.

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“…Urothelial TRPV1 expression and sensitivity were increased in patients with IDO (45). In women with sensory urgency, TRPV1 mRNA expressed in trigonal mucosa was not only increased, but also inversely correlated with the bladder volume at first sensation of filling during cystometry, further indicating that TRPV1 plays a role in premature bladder sensation (191).…”

Section: Capsaicin and Rtxmentioning

confidence: 88%

Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

399

362

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The urothelium, which lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, not only forms a high-resistance barrier to ion, solute and water flux, and pathogens, but also functions as an integral part of a sensory web which receives, amplifies, and transmits information about its external milieu. Urothelial cells have the ability to sense changes in their extracellular environment, and respond to chemical, mechanical and thermal stimuli by releasing various factors such as ATP, nitric oxide, and acetylcholine. They express a variety of receptors and ion channels, including P2X3 purinergic receptors, nicotinic and muscarinic receptors, and TRP channels, which all have been implicated in urothelial-neuronal interactions, and involved in signals that via components in the underlying lamina propria, such as interstitial cells, can be amplified and conveyed to nerves, detrusor muscle cells, and ultimately the central nervous system. The specialized anatomy of the urothelium and underlying structures, and the possible communication mechanisms from urothelial cells to various cell types within the bladder wall are described. Changes in the urothelium/ lamina propria ("mucosa") produced by different bladder disorders are discussed, as well as the mucosa as a target for therapeutic interventions.

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“…Urothelial cells release ATP, NO, or ACh, transmitters that can act on afferent neurons to alter their excitability (6,10,26,30,34,35,44,54). Thus alterations in TRP channel expression or function, which have been reported in pathological conditions (1,2,12,22,37), might lead to altered extracellular levels of neurotransmitters in bladder mucosa and in turn to altered afferent nerve activity and altered bladder function. Indeed, previous studies reported upregulation of ATP release from bladders that are overactive as a result of inflammation (47) or spinal cord injury (45) and increased ATP release from urothelial cells from human patients (51) or cats (11) with interstitial cystitis (for a review, see Ref.…”

Section: Discussionmentioning

confidence: 99%

“…Since the discovery of TRP channels in the urothelium, several studies using intravesical administration of selective agonists (9,23,28,40,50,58), genetically engineered mice lacking specific TRP channels (TRP Ϫ/Ϫ mice) (13,14,28), or investigating the changes in the expression of TRP channels in various pathological conditions (1,22,37) have attempted to establish a role of these channels in bladder function. Intravesical administration of a TRPV1 agonist (capsaicin) (58), TRPA1 agonists (trans-cinnamaldehyde or allyl isothiocyanate) (50), and a TRPM8/TRPA1 agonist (menthol) (40), have excitatory effects on the reflex bladder activity, increasing micturition frequency, and reducing voided volume.…”

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confidence: 99%

Functional TRP and ASIC-like channels in cultured urothelial cells from the rat

Kullmann

Shah²,

Birder³

et al. 2009

American Journal of Physiology-Renal Physiology

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Transient receptor potential (TRP) and acid-sensing ion channels (ASIC) are molecular detectors of chemical, mechanical, thermal, and nociceptive stimuli in sensory neurons. They have been identified in the urothelium, a tissue considered part of bladder sensory pathways, where they might play a role in bladder function. This study investigated functional properties of TRP and ASIC channels in cultured urothelial cells from the rat using patch-clamp and fura 2 Ca 2ϩ imaging techniques. The TRPV4 agonist 4␣-phorbol-12,13 didecanoate (4␣-PDD; 1-5 M) and the TRPA1/TRPM8 agonist icilin (50 -100 M) elicited transient currents in a high percentage of cells (Ͼ70%). 4␣-PDD responses were suppressed by the TRPV4 antagonist HC-010961 (10 M). The TRPV1 agonist capsaicin (1-100 M) and the TRPA1/TRPM8 agonist menthol (5-200 M) elicited transient currents in a moderate percentage of cells (ϳ25%). All of these agonists increased intracellular calcium concentration ([Ca 2ϩ ]i). Most cells responded to more than one TRP agonist (e.g., capsaicin and 4␣-PDD), indicating coexpression of different TRP channels. In the presence of the TRPV1 antagonist capsazepine (10 M), changes in pH induced by HCl elicited ionic currents (pH 5.5) and increased [Ca 2ϩ ]i (pH 6.5) in ϳ50% of cells. Changes in pH using acetic acid (pH 5.5) elicited biphasic-like currents. Responses induced by acid were sensitive to amiloride (10 M). In summary, urothelial cells express multiple TRP and ASIC channels, whose activation elicits ionic currents and Ca 2ϩ influx. These "neuron-like" properties might be involved in transmitter release, such as ATP, that can act on afferent nerves or smooth muscle to modulate their responses to different stimuli. bladder; fura 2 calcium imaging; patch clamp TRANSIENT RECEPTOR POTENTIAL (TRP) channels are nonselective cation channels that function as sensors for various stimuli, including temperature, mechanical stretch, or chemicals (2, 53). They are highly expressed in primary sensory neurons, where they play a critical role in nociception, mechano-, and thermosensation. In these neurons, distinct sets of TRP channels are coexpressed in different populations of cells. This differential pattern of expression confers functional heterogeneity to primary sensory neurons, and it is the basis for detection of sensory information (8,16,31,32,53). TRPV1 is a capsaicin/heat/pH-sensitive channel (16,17); TRPV4 is an osmotic/temperature/mechanical and shear stress detector (24, 36); TRPM8 is a cold (Ͻ22-26°C)/menthol/icilin-activated channel (38, 41); and TRPA1 is a noxious cold-sensitive channel (Ͻ17°C), also sensitive to cinnamaldehyde, mustard oil, menthol, and icilin (4, 49).Immunohistochemistry and RT-PCR identified several TRP channels including TRPV1, TRPV4, TRPM8, and TRPA1 in the urothelium, a specialized epithelial tissue believed to be involved in the detection of chemical and mechanical information and the generation of sensory input from the bladder to the spinal cord (2, 3, 12, 13, 22-24, 28, 39, 48, 50). Since the di...

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The molecular basis of urgency: regional difference of vanilloid receptor expression in the human urinary bladder

Abstract: The symptoms of SU were associated with the increased expression of TRPV1 mRNA in the trigonal mucosa. No upregulation or regional differences of TRPV1 mRNA were seen in IDO patients. TRPV1 may play a role in SU and premature first bladder sensation on filling.

Cited by 71 publications

References 33 publications

Resiniferatoxin and botulinum toxin type A for treatment of lower urinary tract symptoms

Resiniferatoxin and botulinum toxin type A for treatment of lower urinary tract symptoms

Urothelial Signaling

Functional TRP and ASIC-like channels in cultured urothelial cells from the rat

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