title: Supraspinal and spinal effects of L-trans-PDC, an inhibitor of glutamate transporter, on the micturition reflex in rats.
abstract: OBJECTIVE
  Glutamate is a major excitatory transmitter in the central nervous system, controlling lower urinary tract function. Five types of glutamate transporters such as GLAST (EAAT1), GLT-1 (EAAT2), EAAC-1 (EAAT3), EAAT4, and EAAT5 have been cloned so far. In the current study we tested whether L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC), a non-selective inhibitor of glutamate transporters that increases endogenous glutamate concentration, can affect the micturition reflex in urethane anesthetized rats.
  
  
  METHODS
  Continuous cystometrograms (CMG, 0.04 ml/min infusion rate) were performed in two groups of urethane-anesthetized rats. A group of 18 rats was used for intrathecal administration of 1-10 µg of L-trans-PDC via an intrathecal catheter. In the second group of 18 rats, 1-10 µg of L-trans-PDC were administered intracerebroventricularly via a catheter inserted into the lateral ventricle. Micturition parameters were recorded and compared before and after drug administration.
  
  
  RESULTS
  Intrathecal administration of L-trans-PDC at 1, 3, and 10 µg (n = 6 per dose) increased intercontraction intervals in dose dependent fashion, but did not affect postvoid residual or basal pressure at any doses tested. Intracerebroventricular administration of L-trans-PDC at 1, 3, and 10 µg (n = 6 per dose) also increased intercontraction intervals in dose dependent fashion, but did not affect postvoid residual or basal pressure at any doses tested.
  
  
  CONCLUSIONS
  The current results show that, in urethane-anesthetized rats, suppression of glutamate transporters by L-trans-PDC has an inhibitory effect on the micturition reflex at supraspinal and spinal sites, possibly via activation of glutamate-mediated inhibitory pathways.
authors.affiliation: Department of Urology, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Honda
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hikita
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hinata
authors.forename: Kuniyasu
authors.initials: K
authors.lastname: Muraoka
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takenaka
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018686:Anesthetics, Intravenous; D000818:Animals; D003998:Dicarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D057967:Infusions, Intraventricular; D060186:Infusions, Spinal; D009119:Muscle Contraction / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D014179:Neurotransmitter Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D013127:Spinal Nerves / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014520:Urethane; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation; D014554:Urination / Q000187:drug effects*
chemical_list: D027322:Amino Acid Transport System X-AG; D018686:Anesthetics, Intravenous; D003998:Dicarboxylic Acids; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D014520:Urethane; D018698:Glutamic Acid; C083486:pyrrolidine-2,4-dicarboxylic acid