Advanced

Effects of resiniferatoxin desensitization of capsaicin-sensitive afferents on detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP in conscious rats

Zhang, XY; Igawa, Y; Ishizuka, O; Nishizawa, O and Andersson, Karl-Erik LU (2003) In Naunyn-Schmiedeberg's Archives of Pharmacology 367(5). p.473-479
Abstract
Recent studies have provided evidence for a major role of urothelially released ATP acting on a subpopulation of pelvic afferent nerves in mechano-afferent transduction in the bladder. We investigated whether desensitization of capsaicin-sensitive nerve fibres by systemic resiniferatoxin (RTX)-pretreatment can counteract the detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP. Cystometric investigations were performed on awake female Sprague-Dawley rats before and 24 h after injection of RTX (0.3 mg/kg s.c.) or vehicle. The effects of intravesically instilled ATP (0.1 or 1.0 mM), capsaicin (30 muM) or acetic acid (pH 4.0) were compared with those of intravesical saline. RTX, but not its vehicle, significantly... (More)
Recent studies have provided evidence for a major role of urothelially released ATP acting on a subpopulation of pelvic afferent nerves in mechano-afferent transduction in the bladder. We investigated whether desensitization of capsaicin-sensitive nerve fibres by systemic resiniferatoxin (RTX)-pretreatment can counteract the detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP. Cystometric investigations were performed on awake female Sprague-Dawley rats before and 24 h after injection of RTX (0.3 mg/kg s.c.) or vehicle. The effects of intravesically instilled ATP (0.1 or 1.0 mM), capsaicin (30 muM) or acetic acid (pH 4.0) were compared with those of intravesical saline. RTX, but not its vehicle, significantly increased threshold pressure, voiding interval, micturition volume and bladder capacity. In the vehicle-pretreated rats, intravesical instillation of capsaicin or acetic acid significantly decreased voiding interval, micturition volume, and bladder capacity. However, in the RTX-pretreated rats, neither capsaicin nor acetic acid affected any parameter. On the other hand, intravesical ATP (0.1 mM) significantly decreased voiding interval and micturition volume in both groups of animals. At 1.0 mM, ATP also increased basal pressure and decreased the pressure threshold for micturition in both groups. The present results support the view that increased extracellular ATP has a role in mechano-afferent transduction in the rat bladder and that ATP-induced facilitation of the micturition reflex is mediated, at least partly, by nerves other than capsaicin-sensitive afferent nerves. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
urinary bladder, P2X(2/3), VR1, rat, mechano-afferent transduction
in
Naunyn-Schmiedeberg's Archives of Pharmacology
volume
367
issue
5
pages
473 - 479
publisher
Springer
external identifiers
  • wos:000183797000006
  • pmid:12700886
  • scopus:0038459181
ISSN
0028-1298
DOI
language
English
LU publication?
yes
id
21204d8c-81ae-4afc-9bd6-d598d455d20d (old id 306999)
date added to LUP
2007-09-24 15:39:11
date last changed
2018-05-29 10:43:52
@article{21204d8c-81ae-4afc-9bd6-d598d455d20d,
  abstract     = {Recent studies have provided evidence for a major role of urothelially released ATP acting on a subpopulation of pelvic afferent nerves in mechano-afferent transduction in the bladder. We investigated whether desensitization of capsaicin-sensitive nerve fibres by systemic resiniferatoxin (RTX)-pretreatment can counteract the detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP. Cystometric investigations were performed on awake female Sprague-Dawley rats before and 24 h after injection of RTX (0.3 mg/kg s.c.) or vehicle. The effects of intravesically instilled ATP (0.1 or 1.0 mM), capsaicin (30 muM) or acetic acid (pH 4.0) were compared with those of intravesical saline. RTX, but not its vehicle, significantly increased threshold pressure, voiding interval, micturition volume and bladder capacity. In the vehicle-pretreated rats, intravesical instillation of capsaicin or acetic acid significantly decreased voiding interval, micturition volume, and bladder capacity. However, in the RTX-pretreated rats, neither capsaicin nor acetic acid affected any parameter. On the other hand, intravesical ATP (0.1 mM) significantly decreased voiding interval and micturition volume in both groups of animals. At 1.0 mM, ATP also increased basal pressure and decreased the pressure threshold for micturition in both groups. The present results support the view that increased extracellular ATP has a role in mechano-afferent transduction in the rat bladder and that ATP-induced facilitation of the micturition reflex is mediated, at least partly, by nerves other than capsaicin-sensitive afferent nerves.},
  author       = {Zhang, XY and Igawa, Y and Ishizuka, O and Nishizawa, O and Andersson, Karl-Erik},
  issn         = {0028-1298},
  keyword      = {urinary bladder,P2X(2/3),VR1,rat,mechano-afferent transduction},
  language     = {eng},
  number       = {5},
  pages        = {473--479},
  publisher    = {Springer},
  series       = {Naunyn-Schmiedeberg's Archives of Pharmacology},
  title        = {Effects of resiniferatoxin desensitization of capsaicin-sensitive afferents on detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP in conscious rats},
  url          = {http://dx.doi.org/},
  volume       = {367},
  year         = {2003},
}