title: Functional role of the transient receptor potential melastatin 8 (TRPM8) ion channel in the urinary bladder assessed by conscious cystometry and ex vivo measurements of single-unit mechanosensitive bladder afferent activities in the rat.
abstract: OBJECTIVE
  To evaluate the role of the transient receptor potential melastatin 8 (TRPM8) channel on bladder mechanosensory function by using L-menthol, a TRPM8 agonist, and RQ-00203078 (RQ), a selective TRPM8 antagonist.
  
  
  METHODS
  Female Sprague-Dawley rats were used. In conscious cystometry (CMG), the effects of intravesical instillation of L-menthol (3 mm) were recorded after intravenous (i.v.) pretreatment with RQ (3 mg/kg) or vehicle. The direct effects of RQ on conscious CMG and deep body temperature were evaluated with cumulative i.v. administrations of RQ at 0.3, 1, and 3mg/kg. Single-unit mechanosensitive bladder afferent activities (SAAs) were monitored in a newly established ex vivo rat bladder model to avoid systemic influences of the drugs. Recordings were performed after cumulative intra-aortic administration of RQ (0.3 and 3 mg/kg) with or without intra-vesical L-menthol instillation (3 mm).
  
  
  RESULTS
  Intravesical L-menthol decreased bladder capacity and voided volume, which was counteracted by RQ-pretreatment. RQ itself increased bladder capacity and voided volume, and lowered deep body temperature in a dose-dependent manner. RQ decreased mechanosensitive SAAs of C-fibres, and inhibited the activation of SAAs induced by intravesical L-menthol.
  
  
  CONCLUSIONS
  Our results suggest that TRPM8 channels have a role in activation of bladder afferent pathways during filling of the bladder in the normal rat. This effect seems, at least partly, to be mediated via mechanosensitive C-fibres.
authors.affiliation: Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.|Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Aizawa
authors.affiliation: Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.|Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Rino
authors.initials: R
authors.lastname: Sugiyama
authors.affiliation: RaQualia Pharma Inc., Nagoya, Japan.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: RaQualia Pharma Inc., Nagoya, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: RaQualia Pharma Inc., Nagoya, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Tajimi
authors.affiliation: Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuhara
authors.affiliation: Department of Urology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
authors.affiliation: Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: Aarhus Institute of Advanced Studies, Aarhus University, Aarhus, Denmark.
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.affiliation: Department of Continence Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
mesh_terms: D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D005260:Female; D007473:Ion Channels / Q000187:drug effects; D008610:Menthol / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D050053:TRPM Cation Channels / Q000502:physiology*; D001743:Urinary Bladder / Q000502:physiology*; D064804:Urological Agents / Q000494:pharmacology
chemical_list: D007473:Ion Channels; D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat; D064804:Urological Agents; D008610:Menthol
keywords: TRPM8 channel; afferent; detrusor function; rat