title: Spinal glycine transporter-1 inhibition influences the micturition reflex in urethane-anesthetized rats.
abstract: OBJECTIVE
  Glycine is an inhibitory neurotransmitter in the central nervous system. So far, two types of glycine transporters (GlyTs), GlyT-1 and GlyT-2, have been cloned. The aim of this study is to investigate the effects of a selective GlyT-1 inhibitor that can increase endogenous glycine concentration on the micturition reflex in urethane-anesthetized rats.
  
  
  METHODS
  Continuous cystometrograms (0.04 ml/min) were performed in female Sprague-Dawley rats (232-265 g) under urethane anesthesia. After stable micturition cycles were established, ALX5407, a selective GlyT-1 inhibitor, was administered intrathecally or intracerebroventricularly to evaluate changes in bladder activity. Cystometric parameters were recorded and compared before and after drug administration.
  
  
  RESULTS
  Intrathecal administration of ALX5407 (1, 3, 10 and 30 μg) increased intercontraction intervals at doses of 3 μg or higher in a dose-dependent fashion. Intrathecal administration of ALX5407 (1, 3, 10 and 30 μg) also increased pressure threshold at doses of 3 μg or higher in a dose-dependent fashion. However, when ALX5407 (1, 3, 10 and 30 μg) was administered intracerebroventricularly, there were no significant changes in intercontraction intervals, pressure threshold, maximum voiding pressure or baseline pressure or post-void residual urine volume at any doses tested.
  
  
  CONCLUSIONS
  The results of our study indicate that GlyT-1 plays an important role in the modulation of micturition. Furthermore, these findings indicate that in urethane-anesthetized rats suppression of GlyT-1 can inhibit the micturition reflex at the spinal cord level. Thus, GlyT-1 could be a potential target for the treatment of bladder dysfunction such as overactive bladder.
authors: Department of Urology, Tottori University Faculty of Medicine, 36-1 Nishi, Yonago, 683-8504, Japan.|Department of Urology, University of Pittsburgh School of Medicine, Suite 700 Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA, 15213, USA.
authors: Masashi
authors: M
authors: Honda
authors: Department of Urology, Tottori University Faculty of Medicine, 36-1 Nishi, Yonago, 683-8504, Japan.
authors: Katsuya
authors: K
authors: Hikita
authors: Department of Urology, Tottori University Faculty of Medicine, 36-1 Nishi, Yonago, 683-8504, Japan.
authors: Bunya
authors: B
authors: Kawamoto
authors: Department of Urology, Tottori University Faculty of Medicine, 36-1 Nishi, Yonago, 683-8504, Japan.
authors: Kuniyasu
authors: K
authors: Muraoka
authors: Department of Pharmacology, Kochi University School of Medicine, Okocho Kohasu, Nankoku, 7838505, Japan.
authors: Shogo
authors: S
authors: Shimizu
authors: Department of Pharmacology, Kochi University School of Medicine, Okocho Kohasu, Nankoku, 7838505, Japan.
authors: Motoaki
authors: M
authors: Saito
authors: Department of Urology, Tottori University Faculty of Medicine, 36-1 Nishi, Yonago, 683-8504, Japan.
authors: Takehiro
authors: T
authors: Sejima
authors: Department of Urology, William Beaumont Hospital, 3535 W 13 Mile Rd #404, Royal Oak, MI, 48073, USA.
authors: Michael B
authors: MB
authors: Chancellor
authors: Department of Urology, University of Pittsburgh School of Medicine, Suite 700 Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, PA, 15213, USA. nyos@pitt.edu.
authors: Naoki
authors: N
authors: Yoshimura
authors: Department of Urology, Tottori University Faculty of Medicine, 36-1 Nishi, Yonago, 683-8504, Japan.
authors: Atsushi
authors: A
authors: Takenaka
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007278:Injections, Spinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex; D012521:Sarcosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013116:Spinal Cord / Q000378:metabolism*; D014520:Urethane / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014554:Urination / Q000187:drug effects*
chemical_list: C510369:(R)-(N-(3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl))sarcosine; D018686:Anesthetics, Intravenous; D050487:Glycine Plasma Membrane Transport Proteins; C493266:Slc6a9 protein, rat; D014520:Urethane; D012521:Sarcosine
keywords: Bladder; Glycine; Rats; Spinal cord; Transporter