TRPV1 is involved in stretch‐evoked contractile changes in the rat autonomous bladder model: a study with piperine, a new TRPV1 agonist

Gevaert, Thomas; Vandepitte, Joachim; Hutchings, Graham J.; Vriens, Joris; Nilius, Bernd; Ridder, Dirk De

doi:10.1002/nau.20343

Cited by 39 publications

(31 citation statements)

References 34 publications

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“…Our results from in vitro experiments on detrusor contractility after RTX are similar to other studies that tested spontaneous bladder contractions in isolated whole bladders in response to direct application of a TRPV1 agonist and observed a significantly increased amplitude of bladder contractions (21). Additionally, like in our experiments, RTX also induced an increased response to CCh and a change in contractile pattern [increased bladder contractions were followed by a period of quiescence before generating a new contraction (22)].…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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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“…Diffusion of HCl across the mucosa is unlikely to be responsible for the reduction in contraction, because the supernatant remained at pH 7.4 throughout the experiment. Similarly, diffusion of capsaicin across the mucosa is unlikely to play a role in reducing the contraction, because capsaicin contracts circular muscle (27,29,52), the supernatant of the capsaicinfilled sac inhibited circular muscle contraction, and, in addition, the contraction was almost completely restored by a PAF antagonist. PAF, however, is produced with substance P and CGRP; Fig.…”

Section: Discussionmentioning

confidence: 99%

HCl-activated neural and epithelial vanilloid receptors (TRPV1) in cat esophageal mucosa

Cheng¹,

Monte²,

Ma³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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To test whether transient receptor potential channel vanilloid subfamily member-1 (TRPV1) mediates acid-induced inflammation in the esophagus, a tubular segment of esophageal mucosa was tied at both ends, forming a sac. The sac was filled with 0.01 N HCl (or Krebs buffer for control) and kept in oxygenated Krebs buffer at 37°C. The medium around the sac (supernatant) was collected after 3 h. Supernatant of the HCl-filled sac abolished contraction of esophageal circular muscle strips in response to electric field stimulation. Contraction was similarly abolished by supernatant of mucosal sac filled with the TRPV1 agonist capsaicin (10 Ϫ6 M). These effects were reversed by the selective TRPV1 antagonist 5Ј-iodoresiniferatoxin (IRTX) and by the plateletactivating factor (PAF) receptor antagonist CV9388. Substance P and CGRP levels in mucosa and in supernatant increased in response to HCl, and these increases were abolished by IRTX and by tetrodotoxin (TTX) but not affected by CV9388, indicating that substance P and CGRP are neurally released and PAF independent. In contrast, the increase in PAF was blocked by IRTX but not by TTX. Presence of TRPV1 receptor was confirmed by RT-PCR and by Western blot analysis in whole mucosa and in esophageal epithelial cells enzymatically isolated and sorted by flow cytometry or immunoprecipitated with cytokeratin antibodies. In epithelial cells PAF increased in response to HCl, and the increase was abolished by IRTX. We conclude that HCl-induced activation of TRPV1 receptors in esophageal mucosa causes release of substance P and CGRP from neurons and release of PAF from epithelial cells. smooth muscle; signal transduction; platelet-activating factor TRANSIENT RECEPTOR POTENTIAL channel vanilloid subfamily member-1 (TRPV1, also known as VR1) was originally described in primary sensory neurons as a receptor for capsaicin and related natural irritants (collectively referred to as vanilloids) (61). TRPV1 is a nonselective cation channel expressed by several cell types including sensory nerves. It is activated by heat, by the pungent ingredient of chili peppers, capsaicin, or by endogenous hydrogen ions released in tissues during inflammation (61) or present in gastric reflux. TRPV1 is now believed to function as a molecular integrator of noxious stimuli, including acids, heat, pollutants with negative electric charge, and endogenous proinflammatory substances (23). TRPV1 activation in primary afferent neurons evokes the sensation of burning pain and induces neurogenic inflammation by the release of substance P and calcitonin gene-related peptide (CGRP) (65, 66). Upregulated TRPV1 expression has been demonstrated in disease states such as inflammatory bowel disease (66) and irritable bowel syndrome (15) and, more recently, in esophageal submucosal neurons of esophagitis patients (5, 41).TRPV1-associated "neurogenic inflammation" has been examined in several systems, particularly in the airways, and to a lesser extent in the digestive tract. In the digestive tract most publications have ...

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“…However, capsaicin-evoked TRPV1 activation in the rat and mouse in vivo leads to a decrease in ICI, in both awake and anesthetized states, with no change in contraction amplitude (Maggi et al, 1984). In the excised rat bladder, TRPV1 activation increases contraction amplitude (Gevaert et al, 2007). The distension-evoked reflex bladder contraction seems to be reduced selectively in the anesthetized state in mice lacking TRPV1.…”

Section: Expression and Function Of Urinary Bladder Urothelial Trpv4 233mentioning

confidence: 97%

Activation of Urothelial Transient Receptor Potential Vanilloid 4 by 4α-Phorbol 12,13-Didecanoate Contributes to Altered Bladder Reflexes in the Rat

Birder

Kullmann

Lee

et al. 2007

J Pharmacol Exp Ther

130

144

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The ion channel transient receptor potential vanilloid (TRPV) 4 can be activated by hypo-osmolarity, heat, or certain lipid compounds. Here, we demonstrate expression of functional TRPV4 protein in the urothelium lining the renal pelvis, ureters, urinary bladder, and urethra. Exposure of cultured rat urothelial cells from the urinary bladder to the TRPV4-selective agonist 4␣-phorbol 12,13-didecanoate (4␣-PDD) promoted Ca 2ϩ influx, evoked ATP release, and augmented the ATP release evoked by hypo-osmolarity. In awake rats during continuous infusion cystometrograms, intravesical administration of 4␣-PDD (10 -100 M) increased maximal micturition pressure by 51%, specifically by augmenting the portion of each intravesical pressure wave that follows high-frequency urethral oscillations and voiding. This unusual pharmacological effect was prevented by intravesical pretreatment with the nonselective ATP receptor antagonist, pyridoxal phosphate-6-azophenyl-2Ј,4Ј-disulfonic acid (100 M), systemic treatment with the selective P2X 3 purinergic antagonist 5- ([(3-phenoxybenzyl)[1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]carbonyl)-1,2,4-benzenetricarboxylic acid (A317491) (250 mol/kg), or urethane anesthesia, but was unaffected by capsaicin pretreatment (100 mg/kg s.c.) or denervation of the urethral sphincter. 4␣-PDD (1-100 M) did not alter the contractility to electrical stimulation of excised bladder strips. We conclude that activation of urothelial TRPV4 by 4␣-PDD and release of mediators such as ATP trigger a novel neural mechanism that regulates the late phase of detrusor muscle contraction after micturition. These data raise the possibility that TRPV4 channels in the urothelium could contribute to abnormal bladder activity.

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TRPV1 is involved in stretch‐evoked contractile changes in the rat autonomous bladder model: a study with piperine, a new TRPV1 agonist

Abstract: We found evidence for acute and prolonged effects of PIP on bladder contractility, which seem to be mediated through TRPV1. Furthermore, we found evidence for involvement of TRPV1 in afferent signaling of mechanical stimuli.

Cited by 39 publications

References 34 publications

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

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

HCl-activated neural and epithelial vanilloid receptors (TRPV1) in cat esophageal mucosa

Activation of Urothelial Transient Receptor Potential Vanilloid 4 by 4α-Phorbol 12,13-Didecanoate Contributes to Altered Bladder Reflexes in the Rat

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