title: Functional roles of transient receptor potential melastatin 8 (TRPM8) channels in the cold stress-induced detrusor overactivity pathways in conscious rats.
abstract: OBJECTIVE
  We determined if transient receptor potential melastatin 8 (TRPM8) channels are involved in the detrusor overactivity induced by menthol, or exposure to low temperature (LT).
  
  
  METHODS
  Two days prior to cystometric investigation, the bladders of 10-week-old Sprague-Dawley rats were cannulated to measure bladder pressure. After a 20 min baseline cystometry period, the TRPM8 channel antagonist, N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide (BCTC), or vehicle, was administered through a jugular vein catheter (n = 6). A 90% menthol solution was sprayed onto bare leg skin once every 5 min for 20 min, and then cystometric measurements were repeated. After a 30-min recovery period, the rats were intravenously administered 0.1 µmol/kg BCTC. Five minutes later, they were again sprayed and cystometry recorded. In separate experiments, cannulated rats were intravenously administered 0.001, 0.01, or 0.1 µmol/kg BCTC (n = 6 each dose). Five minutes later, they were exposed to LT (4 ± 2°C) for 20 min of cystometry.
  
  
  RESULTS
  Menthol spray decreased voiding interval, micturition volume, and bladder capacity in the BCTC-free rats. However after BCTC administration, these effects were prevented. Exposure to LT elicited detrusor overactivity that caused decreased voiding interval, micturition volume, and bladder capacity. However, at 0.01 and 0.1 µmol/kg, BCTC inhibited this cold stress-induced detrusor overactivity.
  
  
  CONCLUSIONS
  Since the TRPM8 channel agonist, BCTC, inhibited detrusor overactivity in rats sprayed with the TRPM8 channel agonist, menthol, and the drug also inhibited cold stress-induced detrusor overactivity, we conclude that TRPM8 channels mediate, at least partially, detrusor overactivity elicited by exposure to LT.
authors.affiliation: Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lei
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishizuka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Imamura
authors.forename: Wataru
authors.initials: W
authors.lastname: Noguchi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamagishi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kurizaki
authors.forename: Gautam Silwal
authors.initials: GS
authors.lastname: Sudha
authors.forename: Tomoka
authors.initials: T
authors.lastname: Hosoda
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishizawa
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D003080:Cold Temperature; D003243:Consciousness; D004195:Disease Models, Animal; D005260:Female; D000432:Methanol; D011312:Pressure; D011719:Pyrazines / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation*; D053201:Urinary Bladder, Overactive / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D014554:Urination; D014563:Urodynamics
chemical_list: C475772:N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide; D011719:Pyrazines; D011725:Pyridines; D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat; D000432:Methanol