title: Melatonin increases bladder capacity via GABAergic system and decreases urine volume in rats.
abstract: OBJECTIVE
  Impaired melatonin production is involved in disruption of the normal circadian pattern of sleep, which leads to nocturia in older adults. Melatonin improves nocturia. We hypothesized that melatonin could alleviate urinary frequency by suppressing the brain micturition center. We investigated the central contribution of melatonin to bladder function and urine volume.
  
  
  METHODS
  Cystometry was done in conscious female Sprague-Dawley rats (Japan SLC, Hamamatsu, Japan). We examined the effect of melatonin alone (4.3 x 10(-1) to 4.3 x 10 pmol intracerebroventricularly) or with the gamma-aminobutyric acid(A) antagonist bicuculline (5.0 x 10(-5) mg/kg intravenously) on bladder function. The influence of melatonin (4.3 x 10 pmol intracerebroventricularly) on urine volume was investigated in water loaded rats. Blood samples were collected to determine antidiuretic hormone, atrial natriuretic peptide and brain natriuretic peptide 4 hours after melatonin administration.
  
  
  RESULTS
  Melatonin significantly increased bladder capacity dose dependently by 27.0%, 40.8% and 63.5% at 4.3 x 10(-1), 4.3 and 4.3 x 10 pmol, respectively, but had no significant effect on bladder contraction pressure. Bicuculline inhibited the melatonin induced increases in bladder capacity. Melatonin decreased urine volume in water loaded rats but plasma antidiuretic hormone, atrial natriuretic peptide and bladder contraction pressure were not changed.
  
  
  CONCLUSIONS
  Results suggest that melatonin increases bladder capacity via gamma-aminobutyric acid(A) receptor in the brain and decreases urine volume. Thus, melatonin could be beneficial for nocturia via a central nervous system effect.
authors.affiliation: Department of Urology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan. ymatsuda@u-fukui.ac.jp
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsuta
authors.forename: Anwar
authors.initials: A
authors.lastname: Yusup
authors.forename: Kazuya
authors.initials: K
authors.lastname: Tanase
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ishida
authors.forename: Hironobu
authors.initials: H
authors.lastname: Akino
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokoyama
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001640:Bicuculline / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D008550:Melatonin / Q000494:pharmacology*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects*; D014546:Urinary Catheterization; D014554:Urination / Q000187:drug effects*; D014563:Urodynamics / Q000187:drug effects*; D014667:Vasopressins / Q000097:blood
chemical_list: D018755:GABA Agonists; D014667:Vasopressins; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D008550:Melatonin; D001640:Bicuculline