TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications

Avelino, António; Cruz, Francisco

doi:10.1007/s00210-006-0073-2

Cited by 158 publications

(136 citation statements)

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“…In urothelial cells isolated from TRPV1 2/2 mice, ATP release caused by hypotonic stimuli is markedly diminished, and the mutants have a higher frequency of low-amplitude, non-voiding bladder contractions than their wild-type littermates (Birder et al 2002). According to other independent studies, the frequencies of reflex bladder contractions of TRPV1 1/1 and TRPV1 2/2 mice were exactly the same (Avelino and Cruz 2006).…”

Section: Discussionmentioning

confidence: 71%

“…In single-unit bladder nerve recordings, low-threshold neuronal responses were attenuated in TRPV1 2/2 mice compared with the TRPV1 1/1 littermates, whereas high-threshold sensitivity was unchanged (Daly et al 2007), suggesting that those neuronal TRPV1 channels in the suburothelium seem to be needed for the normal excitability of low-threshold bladder fibers. The neuronal TRPV1 is also likely to have pathophysiological roles, contributing to overactive bladder and pain (Avelino and Cruz 2006).…”

Section: Discussionmentioning

confidence: 99%

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Differential Localizations of the Transient Receptor Potential Channels TRPV4 and TRPV1 in the Mouse Urinary Bladder

Yamada

Ugawa

Ueda

et al. 2008

J Histochem Cytochem.

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S U M M A R Y We studied the localization and physiological functions of the transient receptor potential (TRP) channels TRPV1 (TRP vanilloid 1) and TRPV4 (TRP vanilloid 4) in the mouse bladder, because both channels are thought to be mechanosensors for bladder distention. RT-PCR specifically amplified TRPV4 transcripts from the urothelial cells, whereas TRPV1 transcripts were barely detectable. ISH experiments showed that TRPV4 transcripts were abundantly expressed in the urothelium, whereas TRPV1 transcripts were not detectable in the urothelial cells. Immunoblotting and IHC studies showed that TRPV4 proteins were mainly localized at the basal plasma membrane domains of the basal urothelial cells. In contrast, TRPV1-immunoreactivities were found not in the urothelial cells but in the nerve fibers that innervate the urinary bladder. In Ca 21-imaging experiments, 4a-phorbol 12,13-didecanoate, a TRPV4 agonist, and hypotonic stimuli induced significant increases in intracellular calcium ion concentration ([Ca 21 ] i ) in isolated urothelial cells, whereas capsaicin, a TRPV1 agonist, showed no marked effect on the cells. These findings raise the possibility that, in mouse urothelial cells, TRPV4 may contribute to the detection of increases in intravesical pressure related to the micturition reflex. (J Histochem Cytochem 57:277-287, 2009)

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Differential Localizations of the Transient Receptor Potential Channels TRPV4 and TRPV1 in the Mouse Urinary Bladder

Yamada

Ugawa

Ueda

et al. 2008

J Histochem Cytochem.

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“…In this study, we compared detrusor contractility in vitro in the absence of extrinsic neural, hormonal, or immunological factors with in vivo bladder function using dynamic cystometric evaluation. TRPV1 receptors are broadly expressed in the gastrointestinal tract and genitourinary system (3,4,17,18,29). In humans, TRPV1 mRNA was detected in the prostate, testis, penis, bladder, and extrinsic sensory neurons innervating these organs (42).…”

Section: Discussionmentioning

confidence: 99%

“…TRPV1 agonists are well known for causing prolonged desensitization of sensory neurons and fibers followed by an extended refractory period and reduced sensitivity to subsequent noxious stimuli (4). The ability of vanilloids to reduce pelvic pain was tested in patients with painful bladder syndrome/interstitial cystitis (15,35) and in patients with urge incontinence associated with refractory detrusor overactivity (25,41).…”

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confidence: 99%

Acute colonic inflammation triggers detrusor instability via activation of TRPV1 receptors in a rat model of pelvic organ cross-sensitization

Asfaw

Hypolite

Northington

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Asfaw TS, Hypolite J, Northington GM, Arya LA, Wein AJ, Malykhina AP. Acute colonic inflammation triggers detrusor instability via activation of TRPV1 receptors in a rat model of pelvic organ cross-sensitization. Am J Physiol Regul Integr Comp Physiol 300: R1392-R1400, 2011. First published April 6, 2011; doi:10.1152/ajpregu.00804.2010.-Chronic pelvic pain of unknown etiology is a common clinical condition and may develop as a result of cross-sensitization in the pelvis when pathological changes in one of the pelvic organs result in functional alterations in an adjacent structure. The aim of the current study was to compare transient receptor potential vanilloid 1 (TRPV1) activated pathways on detrusor contractility in vivo and in vitro using a rat model of pelvic organ cross-sensitization. Four groups of male Sprague-Dawley rats (N ϭ 56) were included in the study. Animals received intracolonic saline (control), resiniferatoxin (RTX, TRPV1 agonist, 10 Ϫ7 M), 2,4,6-trinitrobenzene sulfonic acid (TNBS, colonic irritant), or double treatment (RTX followed by TNBS). Detrusor muscle contractility was assessed under in vitro and in vivo conditions. Intracolonic RTX increased the contractility of the isolated detrusor in response to electric field stimulation (EFS) by twofold (P Յ 0.001) and enhanced the contractile response of the bladder smooth muscle to carbachol (CCh). Acute colonic inflammation reduced detrusor contractility upon application of CCh in vitro, decreased bladder capacity by 28.1% (P Յ 0.001), and reduced micturition volume by 60% (P Յ 0.001). These changes were accompanied by an increased number of nonmicturition contractions from 3.7 Ϯ 0.7 to 15 Ϯ 2.7 (N ϭ 6 in both groups, P Յ 0.001 vs. control). Desensitization of intracolonic TRPV1 receptors before the induction of acute colitis restored the response of isolated detrusor strips to CCh but not to EFS stimulation. Cystometric parameters were significantly improved in animals with double treatment and approximated the control values. Our data suggest that acute colonic inflammation triggers the occurrence of detrusor instability via activation of TRPV1-related pathways. Comparison of the results obtained under in vitro vs. in vivo conditions provides evidence that intact neural pathways are critical for the development of an overactive bladder resulting from pelvic organ cross talk. neurogenic inflammation; chronic pelvic pain; detrusor; contractility COMORBIDITY OF CLINICAL CONDITIONS characterized by chronic pelvic pain (CPP) has recently gained extra attention from physicians and scientists. Painful bladder syndrome/interstitial cystitis, irritable bowel syndrome, nonbacterial prostatitis/CPP syndrome, vulvodynia, and dysmenorrhea form a group of functional disorders with CPP of unknown etiology with the rate of concurrent diagnoses reaching up to 30 -40% (2, 37).Limited understanding of the causes, underlying mechanisms, and symptomatic complexity in patients with multidimensional pelvic pain make CPP disorders extremely difficult to cure. Cli...

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“…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. However, these studies often cannot distinguish between actions on urothelial or neuronal TRP channels because the agonists can penetrate through the urothelium and act on the adjacent nerves, which express similar channels.Knockout mice have provided evidence for a role of TRPV1 (3,13,14) and of TRPV4 (28) in bladder function. Using TRPV1 Ϫ/Ϫ mice and cultured urothelial cells, it has been shown that urothelial TRPV1 is involved in stretch-evoked ATP release (13,14).…”

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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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TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications

Cited by 158 publications

References 123 publications

Differential Localizations of the Transient Receptor Potential Channels TRPV4 and TRPV1 in the Mouse Urinary Bladder

Differential Localizations of the Transient Receptor Potential Channels TRPV4 and TRPV1 in the Mouse Urinary Bladder

Acute colonic inflammation triggers detrusor instability via activation of TRPV1 receptors in a rat model of pelvic organ cross-sensitization

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

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