Melatonin increases bladder capacity via GABAergic system and decreases urine volume in rats.
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.
Matsuta
Yosuke
Y
Department of Urology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan. ymatsuda@u-fukui.ac.jp
Yusup
Anwar
A
Tanase
Kazuya
K
Ishida
Hirokazu
H
Akino
Hironobu
H
Yokoyama
Osamu
O
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
D018755:GABA Agonists; D014667:Vasopressins; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D008550:Melatonin; D001640:Bicuculline