Function and expression pattern of TRPM8 in bladder afferent neurons associated with bladder outlet obstruction in rats

Hayashi, Tokumasa; Kondo, Teruyoshi; Ishimatsu, Masaru; Takeya, Mitsue; Igata, Sachiyo; Nakamura, Kei‐ichiro; Matsuoka, Kei

doi:10.1016/j.autneu.2011.05.006

Cited by 24 publications

(19 citation statements)

References 49 publications

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“…The results of the present study using in vivo afferent measurements are in line with those of the previous study, suggesting that antagonizing TRPM8 channels can ameliorate abnormally exaggerated bladder mechano‐afferent transduction. TRPM8 channels are expressed on the urothelium and suburothelial nerve fibers in the bladder and also expressed on DRG neurons of rats . Regarding the mechanisms and sites of action of TRPM8 channels in the present study, we require further investigations, and this is a limitation of the present study.…”

Section: Discussionmentioning

confidence: 82%

“…TRPM8 channels are expressed on the urothelium and suburothelial nerve fibers in the bladder 6 and also expressed on DRG neurons of rats. 6,9,21 Regarding the mechanisms and sites of action of TRPM8 channels in the present study, we require further investigations, and this is a limitation of the present study. In addition, previous studies revealed that spinal expression of an immediate early gene, c-fos, one of the functional markers of neural activity, increased dramatically following continuous intravesical instillation of AA compared with nonnoxious stimulation of the bladder (saline instillation).…”

Section: Discussionmentioning

confidence: 87%

“…6 We previously reported that TRPM8 channels may have a role in the activation of bladder afferent pathways during bladder filling in normal rats, and this effect was at least partly mediated via mechanosensitive C fibers. 8 In addition, possible contribution of TRPM8 channels has been proposed in pathophysiological conditions such as bladder outlet obstruction in rats 9,10 and bladder pain syndrome and detrusor overactivity in humans. 11,12 Therefore, TRPM8 channels may be involved in the bladder sensory transduction, playing a role in the abnormal activation in hypersensitive bladder disorders.…”

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confidence: 99%

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KPR‐2579, a novel TRPM8 antagonist, inhibits acetic acid‐induced bladder afferent hyperactivity in rats

Aizawa

Fujimori

Kobayashi

et al. 2018

Neurourology and Urodynamics

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 99%

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KPR‐2579, a novel TRPM8 antagonist, inhibits acetic acid‐induced bladder afferent hyperactivity in rats

Aizawa

Fujimori

Kobayashi

et al. 2018

Neurourology and Urodynamics

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“…1). Hayashi et al [21] reported that the MP after menthol treatment was increased by reinforcing the contraction of detrusor muscle or increasing the urethral outlet resistance during the micturition phase. Therefore, menthol probably contributes to the voiding by bladder contraction.…”

Section: Discussionmentioning

confidence: 99%

“…TRPM8 is divided into two groups as a cold temperature- and menthol-sensitive cation channel [21,22]. Activation by cold or agonists (menthol, icilin) induces a transient rise in the intracellular free calcium concentration [23].…”

Section: Introductionmentioning

confidence: 99%

Function of the Cold Receptor (TRPM8) Associated with Voiding Dysfunction in Bladder Outlet Obstruction in Rats

et al. 2012

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PurposeBladder outlet obstruction (BOO) causes storage and voiding dysfunction in the lower urinary tract. We investigated the expression of transient receptor potential cation channel subfamily M member 8 (TRPM8) to evaluate the relationship between TRPM8 expression and overactive bladder (OAB) in a rat model of BOO.MethodsFifty female Sprague-Dawley rats were divided into 4 groups; normal (n=10), normal-menthol (n=10), BOO (n=15), BOO-menthol (n=15). After 3 weeks, cystometry was performed by infusing physiological saline and menthol (3 mM) into the bladder at a slow infusion rate. The histological changes and expression of TRPM8 in the bladder were investigated by Masson's trichrome staining, immunofluorescence and reverse transcription-polymerase chain reaction.ResultsCystometry showed that the intercontraction interval (ICI; 428.2±23.4 vs. 880.4±51.2, P<0.001), micturition pressure (MP; 25.7±1.01 vs. 71.80±3.01, P<0.001), and threshold pressure (2.9±0.25 vs. 9.2±1.58, P<0.01) were significantly increased in BOO rats. The bladder wall was significantly dilated compared with the control. Detrusor muscle hypertrophy and a thick mucosa layer were observed in BOO bladder. After menthol treatment, ICIs were decreased and MPs were increased in the menthol treatment groups. TRPM8-positive cells and mRNA were predominantly increased in the bladder and dorsal root ganglia of all groups compared with the normal group.ConclusionsIncreased bladder wall thickness and proportion of collagen probably affect voiding dysfunction. Furthermore, an increase of TRPM8 expression in BOO may induce entry of Ca2+ from the extracellular space or stores. The increase of Ca2+ probably causes contraction of smooth muscle in BOO. However, OAB symptoms were not observed after menthol treatment although the expression of TRPM8 was abundant in the bladder epithelium after menthol treatment. Although OAB in BOO models may be caused by complex pathways, regulation of TRPM8 presents possibilities for OAB treatment.

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Activation of TRPM8 channel inhibits contraction of the isolated human ureter

Liu

Zhao

et al. 2021

Neurourology and Urodynamics

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Aims:The transient receptor potential melastin-8 (TRPM8) channel is a "cooling" receptor expressed in primary sensory neurons and can be activated by compounds like menthol or icilin. TRPM8 is involved in the regulation of urinary bladder sensory function and contraction, but the role of TRPM8 in the ureter, particularly in the human ureter, is poorly understood. The aim of this study is to examine the effects of TRPM8 activation on human ureter contraction. Methods: Human ureters were acquired from 20 patients undergoing radical nephrectomy. Contractions of ureter strips were recorded by an isometric transducer in the organ bath. Ureteral TRPM8 expression in the human ureter was examined by immunofluorescence and western blot. Results:The two TRPM8 agonists menthol and icilin both reduced the frequency of spontaneous, electrical field stimulation, or neurokinin A-evoked ureteral contractions in a dose-dependent manner. The inhibitory effects were decreased by 10-fold in mucosa-denuded strips. The inhibitory effects of TRPM8 agonists were mimicked by calcitonin gene-related peptide (CGRP), and were blocked by KRP2579 (a TRPM8 antagonist), tetrodotoxin (a sodium channel blocker), olcegepant (BIBN, a CGRP receptor antagonist), SQ22536 (an adenylate cyclase antagonist), or H89 (a nonspecific cAMP-dependent protein kinase A inhibitor). TRPM8 was coexpressed with CGRP on the nerves located in the suburothelial and intermuscular regions and was not expressed in the urothelium. Conclusions: The TRPM8 channel expressed on sensory nerve terminals of the human ureter is involved in the inhibitory sensory neurotransmission and modulate ureter contraction via the CGRP-adenylyl cyclase-protein kinase A pathway. TRPM8 may be involved in stone-induced changes in ureter contraction or pain.

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Function and expression pattern of TRPM8 in bladder afferent neurons associated with bladder outlet obstruction in rats

Cited by 24 publications

References 49 publications

KPR‐2579, a novel TRPM8 antagonist, inhibits acetic acid‐induced bladder afferent hyperactivity in rats

KPR‐2579, a novel TRPM8 antagonist, inhibits acetic acid‐induced bladder afferent hyperactivity in rats

Function of the Cold Receptor (TRPM8) Associated with Voiding Dysfunction in Bladder Outlet Obstruction in Rats

Activation of TRPM8 channel inhibits contraction of the isolated human ureter

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