title: Muscarinic receptors mediate cold stress-induced detrusor overactivity in type 2 diabetes mellitus rats.
abstract: OBJECTIVE
  This study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type 2 diabetes mellitus rats.
  
  
  METHODS
  Ten-week-old female Goto-Kakizaki diabetic rats (n = 12) and Wister Kyoto non-diabetic rats (n = 12) were maintained on a high-fat diet for 4 weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (27 ± 2°C) for 20 min. They were intravenously administered imidafenacin (0.3 mg/kg, n = 6) or vehicle (n = 6). After 5 min, the rats were transferred to a low temperature (4 ± 2°C) for 40 min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M3 and M2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry.
  
  
  RESULTS
  In non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M3 to M2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats.
  
  
  CONCLUSIONS
  Imidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M3 receptors partially mediate cold stress-induced detrusor overactivity.
authors.affiliation: Department of Lower Urinary Tract Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Imamura
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishizuka
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Ogawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamagishi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Tomonori
authors.initials: T
authors.lastname: Minagawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakazawa
authors.forename: Sudha Silwal
authors.initials: SS
authors.lastname: Gautam
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishizawa
mesh_terms: D000818:Animals; D003080:Cold Temperature; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011921:Rats, Inbred WKY; D043585:Receptor, Muscarinic M2 / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics; D043587:Receptor, Muscarinic M3 / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics; D013312:Stress, Physiological / Q000187:drug effects; D053201:Urinary Bladder, Overactive / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects
chemical_list: D007093:Imidazoles; D012333:RNA, Messenger; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; C120953:imidafenacin
keywords: cold stress; detrusor overactivity; diabetic mellitus rat; imidafenacin; muscarinic receptors