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Functional role of central muscarinic receptors for micturition in normal conscious rats

Ishizuka, O; Gu, BJ; Yang, ZX; Nishizawa, O and Andersson, Kenneth LU (2002) In Journal of Urology 168(5). p.2258-2262
Abstract
Purpose: Antimuscarinic agents, which are used in to treat urgency and urge incontinence, have well-known effects on peripheral muscarinic receptors. However, some currently used drugs may have effects on muscarinic receptors in the brain and/or spinal cord involved in voiding control. We tested if muscarinic receptors within the central nervous system mediate a tonic excitatory influence on voiding in rats and if these receptors can be differently influenced by antimuscarinic drugs. Materials and Methods: The effects on cystometrography of intracerebroventricular atropine, oxybutynin, tolterodine and darifenacin were investigated in normal conscious rats. Results: Atropine (0.2 to 2 nmol.) dose dependently affected urodynamic parameters.... (More)
Purpose: Antimuscarinic agents, which are used in to treat urgency and urge incontinence, have well-known effects on peripheral muscarinic receptors. However, some currently used drugs may have effects on muscarinic receptors in the brain and/or spinal cord involved in voiding control. We tested if muscarinic receptors within the central nervous system mediate a tonic excitatory influence on voiding in rats and if these receptors can be differently influenced by antimuscarinic drugs. Materials and Methods: The effects on cystometrography of intracerebroventricular atropine, oxybutynin, tolterodine and darifenacin were investigated in normal conscious rats. Results: Atropine (0.2 to 2 nmol.) dose dependently affected urodynamic parameters. At 2 nmol. in 6 rats the drug decreased voiding pressure (p <0.01), and increased bladder capacity (p <0.001), voided volume (p <0.05) and post-void residual volume (p <0.05). In 6 rats oxybutynin (6 to 40 nmol.) given at a dose of 6 nmol. caused no change in cystometric parameters, while at 20 nmol. the drug decreased voiding pressure (p <0.01). Tolterodine (2 to 20 nmol.) dose dependently changed urodynamic parameters, while at 20 nmol. in 6 rats the drug decreased voiding pressure (p <0.01) and increased bladder capacity (p <0.05) and voided volume (p <0.05). Darifenacin given at a dose of 20 nmol. in 6 rats caused no change in cystometric parameters. Conclusions: Muscarinic receptor mechanisms in the central nervous system mediate a tonic excitatory influence on voiding in rats, while nonsubtype selective antimuscarinic drugs may have an inhibitory effect on these mechanisms. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
central nervous, Sprague-Dawley, rats, muscarinic, urination, receptors, system
in
Journal of Urology
volume
168
issue
5
pages
2258 - 2262
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000178562100127
  • pmid:12394771
  • scopus:0036837459
ISSN
1527-3792
DOI
10.1016/S0022-5347(05)64367-4
language
English
LU publication?
yes
id
d4caacac-36cc-43a4-82c4-5be92dc86bfd (old id 325562)
date added to LUP
2007-10-23 10:43:17
date last changed
2017-01-01 07:19:46
@article{d4caacac-36cc-43a4-82c4-5be92dc86bfd,
  abstract     = {Purpose: Antimuscarinic agents, which are used in to treat urgency and urge incontinence, have well-known effects on peripheral muscarinic receptors. However, some currently used drugs may have effects on muscarinic receptors in the brain and/or spinal cord involved in voiding control. We tested if muscarinic receptors within the central nervous system mediate a tonic excitatory influence on voiding in rats and if these receptors can be differently influenced by antimuscarinic drugs. Materials and Methods: The effects on cystometrography of intracerebroventricular atropine, oxybutynin, tolterodine and darifenacin were investigated in normal conscious rats. Results: Atropine (0.2 to 2 nmol.) dose dependently affected urodynamic parameters. At 2 nmol. in 6 rats the drug decreased voiding pressure (p &lt;0.01), and increased bladder capacity (p &lt;0.001), voided volume (p &lt;0.05) and post-void residual volume (p &lt;0.05). In 6 rats oxybutynin (6 to 40 nmol.) given at a dose of 6 nmol. caused no change in cystometric parameters, while at 20 nmol. the drug decreased voiding pressure (p &lt;0.01). Tolterodine (2 to 20 nmol.) dose dependently changed urodynamic parameters, while at 20 nmol. in 6 rats the drug decreased voiding pressure (p &lt;0.01) and increased bladder capacity (p &lt;0.05) and voided volume (p &lt;0.05). Darifenacin given at a dose of 20 nmol. in 6 rats caused no change in cystometric parameters. Conclusions: Muscarinic receptor mechanisms in the central nervous system mediate a tonic excitatory influence on voiding in rats, while nonsubtype selective antimuscarinic drugs may have an inhibitory effect on these mechanisms.},
  author       = {Ishizuka, O and Gu, BJ and Yang, ZX and Nishizawa, O and Andersson, Kenneth},
  issn         = {1527-3792},
  keyword      = {central nervous,Sprague-Dawley,rats,muscarinic,urination,receptors,system},
  language     = {eng},
  number       = {5},
  pages        = {2258--2262},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Urology},
  title        = {Functional role of central muscarinic receptors for micturition in normal conscious rats},
  url          = {http://dx.doi.org/10.1016/S0022-5347(05)64367-4},
  volume       = {168},
  year         = {2002},
}