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Effects of tiagabine, a gamma-aminobutyric acid re-uptake inhibitor, on normal rat bladder function.

Pehrson, Rikard LU and Andersson, Karl-Erik LU (2002) In Journal of Urology 167(5). p.2241-2246
Abstract
PURPOSE: Previous reports have demonstrated the inhibitory effect of exogenous gamma-aminobutyric acid (GABA) on micturition. In the current study we tested whether tiagabine (Sanofi Synthelab., Newcastle-upon Tyne, United Kingdom), a GABA re-uptake inhibitor increasing endogenous GABA concentrations, would affect micturition in awake rats or influence rat detrusor contraction in vitro. MATERIALS AND METHODS: Nonanesthetized female Sprague-Dawley rats underwent cystometric investigation in a metabolic cage. Micturition was stimulated by infusing saline intravesically. Micturition parameters were recorded and compared before and after drug administration. In vitro the effects of tiagabine on electrical and carbachol induced contractions in... (More)
PURPOSE: Previous reports have demonstrated the inhibitory effect of exogenous gamma-aminobutyric acid (GABA) on micturition. In the current study we tested whether tiagabine (Sanofi Synthelab., Newcastle-upon Tyne, United Kingdom), a GABA re-uptake inhibitor increasing endogenous GABA concentrations, would affect micturition in awake rats or influence rat detrusor contraction in vitro. MATERIALS AND METHODS: Nonanesthetized female Sprague-Dawley rats underwent cystometric investigation in a metabolic cage. Micturition was stimulated by infusing saline intravesically. Micturition parameters were recorded and compared before and after drug administration. In vitro the effects of tiagabine on electrical and carbachol induced contractions in bladder strips were investigated. Furthermore, it was studied whether tiagabine interfered with electrically induced release of acetylcholine. RESULTS: Intravenous administration of 5 and 20 mg. kg.-1 tiagabine in 7 and 9 rats decreased micturition pressure a mean plus or minus standard error of mean of 21% +/- 11% and 42% +/- 9%, and decreased voided volume a mean of 31% +/- 9% and 33% +/- 9%, respectively. At 20 mg. kg.-1 tiagabine intravenously increased post-void residual volume a mean of 300% +/- 120% and decreased bladder capacity a mean of 14% +/- 3%. Tiagabine (100 microg.) intrathecally in 7 rats reduced micturition pressure a mean of 34% +/- 10% and increased bladder capacity a mean of 30% +/- 9% and post-void residual volume a mean of 250% +/- 75%. However, voided volume was not changed. In vitro studies demonstrated that tiagabine attenuated bladder contractions induced by electrical field stimulation to a mean of 69% +/- 6% of controls at 100 microM. but did not affect contractions induced by carbachol. Release studies revealed that tiagabine inhibited electrical induced acetylcholine release to a mean of 82% +/- 5% of controls at 100 microM. CONCLUSIONS: The current results show that tiagabine has an inhibitory action on rat micturition. The site of action may be central and peripheral. (Less)
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published
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keywords
Female, GABA Agonists : pharmacology, Neurotransmitter Uptake Inhibitors : pharmacology, Rats, Nipecotic Acids : pharmacology, Sprague-Dawley, Urination : drug effects, Urodynamics : drug effects, Drug, Dose-Response Relationship, Comparative Study, Bladder : drug effects, Animal
in
Journal of Urology
volume
167
issue
5
pages
2241 - 2246
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000174963900087
  • pmid:11956486
ISSN
1527-3792
DOI
10.1016/S0022-5347(05)65136-1
language
English
LU publication?
yes
id
4a5af93d-fc14-47f4-b145-4def9eb9af66 (old id 107701)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11956486&dopt=Abstract
date added to LUP
2007-07-05 16:00:31
date last changed
2016-04-16 05:00:11
@article{4a5af93d-fc14-47f4-b145-4def9eb9af66,
  abstract     = {PURPOSE: Previous reports have demonstrated the inhibitory effect of exogenous gamma-aminobutyric acid (GABA) on micturition. In the current study we tested whether tiagabine (Sanofi Synthelab., Newcastle-upon Tyne, United Kingdom), a GABA re-uptake inhibitor increasing endogenous GABA concentrations, would affect micturition in awake rats or influence rat detrusor contraction in vitro. MATERIALS AND METHODS: Nonanesthetized female Sprague-Dawley rats underwent cystometric investigation in a metabolic cage. Micturition was stimulated by infusing saline intravesically. Micturition parameters were recorded and compared before and after drug administration. In vitro the effects of tiagabine on electrical and carbachol induced contractions in bladder strips were investigated. Furthermore, it was studied whether tiagabine interfered with electrically induced release of acetylcholine. RESULTS: Intravenous administration of 5 and 20 mg. kg.-1 tiagabine in 7 and 9 rats decreased micturition pressure a mean plus or minus standard error of mean of 21% +/- 11% and 42% +/- 9%, and decreased voided volume a mean of 31% +/- 9% and 33% +/- 9%, respectively. At 20 mg. kg.-1 tiagabine intravenously increased post-void residual volume a mean of 300% +/- 120% and decreased bladder capacity a mean of 14% +/- 3%. Tiagabine (100 microg.) intrathecally in 7 rats reduced micturition pressure a mean of 34% +/- 10% and increased bladder capacity a mean of 30% +/- 9% and post-void residual volume a mean of 250% +/- 75%. However, voided volume was not changed. In vitro studies demonstrated that tiagabine attenuated bladder contractions induced by electrical field stimulation to a mean of 69% +/- 6% of controls at 100 microM. but did not affect contractions induced by carbachol. Release studies revealed that tiagabine inhibited electrical induced acetylcholine release to a mean of 82% +/- 5% of controls at 100 microM. CONCLUSIONS: The current results show that tiagabine has an inhibitory action on rat micturition. The site of action may be central and peripheral.},
  author       = {Pehrson, Rikard and Andersson, Karl-Erik},
  issn         = {1527-3792},
  keyword      = {Female,GABA Agonists : pharmacology,Neurotransmitter Uptake Inhibitors : pharmacology,Rats,Nipecotic Acids : pharmacology,Sprague-Dawley,Urination : drug effects,Urodynamics : drug effects,Drug,Dose-Response Relationship,Comparative Study,Bladder : drug effects,Animal},
  language     = {eng},
  number       = {5},
  pages        = {2241--2246},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Urology},
  title        = {Effects of tiagabine, a gamma-aminobutyric acid re-uptake inhibitor, on normal rat bladder function.},
  url          = {http://dx.doi.org/10.1016/S0022-5347(05)65136-1},
  volume       = {167},
  year         = {2002},
}