Advanced

Transient Receptor Potential A1 (TRPA1) Activity in the Human Urethra-Evidence for a Functional Role for TRPA1 in the Outflow Region.

Gratzke, Christian; Streng, Tomi LU ; Waldkirch, Eginhard; Sigl, Katja; Stief, Christian; Andersson, Karl-Erik LU and Hedlund, Petter LU (2009) In European Urology 55. p.696-704
Abstract
BACKGROUND: A role for the transient receptor potential (TRP) A1 ion channel in rat lower urinary tract (LUT) sensation and disease has been proposed, but in the human LUT no information on TRPA1 activity is available. OBJECTIVES: To investigate the distribution of TRPA1 in the human urethra and to study the effect of TRPA1 agonists on isolated urethral strip preparations. DESIGN, SETTINGS, AND PARTICIPANTS: Urethral specimens were obtained preoperatively from 10 patients and were freshly prepared for Western blot, immunohistochemistry, and functional in vitro investigations. MEASUREMENTS: The expression patterns of TRPA1 were studied with Western blot and immunohistochemistry. The effects of allyl isothiocyanate (AI), cinnamaldehyde (CA),... (More)
BACKGROUND: A role for the transient receptor potential (TRP) A1 ion channel in rat lower urinary tract (LUT) sensation and disease has been proposed, but in the human LUT no information on TRPA1 activity is available. OBJECTIVES: To investigate the distribution of TRPA1 in the human urethra and to study the effect of TRPA1 agonists on isolated urethral strip preparations. DESIGN, SETTINGS, AND PARTICIPANTS: Urethral specimens were obtained preoperatively from 10 patients and were freshly prepared for Western blot, immunohistochemistry, and functional in vitro investigations. MEASUREMENTS: The expression patterns of TRPA1 were studied with Western blot and immunohistochemistry. The effects of allyl isothiocyanate (AI), cinnamaldehyde (CA), and NaHS (donor of H(2)S) on tension of urethral strips were investigated in tissue baths. RESULTS AND LIMITATIONS: TRPA1 immunoreactivity (-IR) was found in nerve fibres in the suburothelial space and was also located to nerve fibres of the muscle layer. Single TRPA1-IR nerves extended into the urothelium. A majority, but not all TRPA1-IR nerves also expressed immunoreactivity for CGRP or TRPV1. In the urothelium, TRPV1 was located to the outer layers whereas TRPA1 was observed in basal urothelial cells. Interspersed between strands of smooth muscle cells of the urethral wall, TRPA1- and vimentin-IR cells containing central nuclei and slender cytoplasmatic extensions were observed. In functional experiments, TRPA1-agonists had no contractile effect in urethral preparations. After precontraction with phenylephrine, AI, CA, and NaHS caused concentration-dependent relaxations of urethral strip preparations. CONCLUSIONS: The localization of TRPA1 to nerves that also express TRPV1 and CGRP, and in urothelial cells and interstitial cells, as well as the findings that TRPA1 agonists can modify tone of urethral preparations, propose a role for TRPA1 in afferent and efferent sensory signaling of the human outflow region. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Urology
volume
55
pages
696 - 704
publisher
Elsevier
external identifiers
  • WOS:000263762200020
  • PMID:18468780
  • Scopus:58849127865
ISSN
1873-7560
DOI
10.1016/j.eururo.2008.04.042
language
English
LU publication?
yes
id
c529fca3-0c44-4113-a742-481eb7536a03 (old id 1154334)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18468780?dopt=Abstract
date added to LUP
2008-06-02 15:49:24
date last changed
2016-11-20 04:24:47
@misc{c529fca3-0c44-4113-a742-481eb7536a03,
  abstract     = {BACKGROUND: A role for the transient receptor potential (TRP) A1 ion channel in rat lower urinary tract (LUT) sensation and disease has been proposed, but in the human LUT no information on TRPA1 activity is available. OBJECTIVES: To investigate the distribution of TRPA1 in the human urethra and to study the effect of TRPA1 agonists on isolated urethral strip preparations. DESIGN, SETTINGS, AND PARTICIPANTS: Urethral specimens were obtained preoperatively from 10 patients and were freshly prepared for Western blot, immunohistochemistry, and functional in vitro investigations. MEASUREMENTS: The expression patterns of TRPA1 were studied with Western blot and immunohistochemistry. The effects of allyl isothiocyanate (AI), cinnamaldehyde (CA), and NaHS (donor of H(2)S) on tension of urethral strips were investigated in tissue baths. RESULTS AND LIMITATIONS: TRPA1 immunoreactivity (-IR) was found in nerve fibres in the suburothelial space and was also located to nerve fibres of the muscle layer. Single TRPA1-IR nerves extended into the urothelium. A majority, but not all TRPA1-IR nerves also expressed immunoreactivity for CGRP or TRPV1. In the urothelium, TRPV1 was located to the outer layers whereas TRPA1 was observed in basal urothelial cells. Interspersed between strands of smooth muscle cells of the urethral wall, TRPA1- and vimentin-IR cells containing central nuclei and slender cytoplasmatic extensions were observed. In functional experiments, TRPA1-agonists had no contractile effect in urethral preparations. After precontraction with phenylephrine, AI, CA, and NaHS caused concentration-dependent relaxations of urethral strip preparations. CONCLUSIONS: The localization of TRPA1 to nerves that also express TRPV1 and CGRP, and in urothelial cells and interstitial cells, as well as the findings that TRPA1 agonists can modify tone of urethral preparations, propose a role for TRPA1 in afferent and efferent sensory signaling of the human outflow region.},
  author       = {Gratzke, Christian and Streng, Tomi and Waldkirch, Eginhard and Sigl, Katja and Stief, Christian and Andersson, Karl-Erik and Hedlund, Petter},
  issn         = {1873-7560},
  language     = {eng},
  pages        = {696--704},
  publisher    = {ARRAY(0xa4f78b0)},
  series       = {European Urology},
  title        = {Transient Receptor Potential A1 (TRPA1) Activity in the Human Urethra-Evidence for a Functional Role for TRPA1 in the Outflow Region.},
  url          = {http://dx.doi.org/10.1016/j.eururo.2008.04.042},
  volume       = {55},
  year         = {2009},
}