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TRPA1 Receptor Induced Relaxation of the Human Urethra Involves TRPV1 and Cannabinoid Receptor Mediated Signals, and Cyclooxygenase Activation

Weinhold, Philipp; Gratzke, Christian; Streng, Tomi; Stief, Christian; Andersson, Karl-Erik LU and Hedlund, Petter LU (2010) In Journal of Urology 183(5). p.2070-2076
Abstract
Purpose: We studied whether TRPA1 agonists interact with sensory and inflammatory signals to relax human urethral smooth muscle. Materials and Methods: Urethral specimens were obtained perioperatively from 19 patients, and prepared for immunohistochemistry and functional experiments. The effects of allyl isothiocyanate, cinnamaldehyde and NaHS were studied in phenylephrine activated preparations combined with capsaicin, capsazepine, N omega-nitro-L-arginine, indomethacin or CP55940. Results: TRPA1, cannabinoid 1 and cannabinoid 2 immunoreactivity was colocalized in nerve fibers of the human urethra. All TRPA1 agonists produced relaxation of phenylephrine contracted urethral preparations. Capsaicin increased relaxant responses to all TRPA1... (More)
Purpose: We studied whether TRPA1 agonists interact with sensory and inflammatory signals to relax human urethral smooth muscle. Materials and Methods: Urethral specimens were obtained perioperatively from 19 patients, and prepared for immunohistochemistry and functional experiments. The effects of allyl isothiocyanate, cinnamaldehyde and NaHS were studied in phenylephrine activated preparations combined with capsaicin, capsazepine, N omega-nitro-L-arginine, indomethacin or CP55940. Results: TRPA1, cannabinoid 1 and cannabinoid 2 immunoreactivity was colocalized in nerve fibers of the human urethra. All TRPA1 agonists produced relaxation of phenylephrine contracted urethral preparations. Capsaicin increased relaxant responses to all TRPA1 agonists. It increased the mean SEM -logIC50 of cinnamaldehyde and NaHS from 4.91 +/- 0.26 to 5.15 +/- 0.22 and 3.27 +/- 0.14 to 3.79 +/- 0.35, and the -logIC30 of allyl isothiocyanate from 3.11 +/- 0.24 to 3.41 +/- 0.26 (each p < 0.05). Capsazepine in 5 preparations, indomethacin in 6 and CP55940 in 5 decreased cinnamaldehyde mediated relaxation by up to 39%, 88% and 89%, respectively. Nw-nitro-L-arginine and urothelial removal had no effect on relaxation by cinnamaldehyde in 5 preparations. Conclusions: Relaxation to TRPA1 agonists in human urethral preparations seem to work in cooperation with TRPV1 mediated signals, are negatively coupled via cannabinoid receptor activation and involve cyclooxygenase products. Urothelial TRPA1 signals may not be important to regulate normal human urethral smooth muscle tone. This does not exclude a role in the initiation of afferent activity normally and in disease states. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
protein, human, TRPV1, TRPA1 protein, muscle relaxation, urethra, urothelium
in
Journal of Urology
volume
183
issue
5
pages
2070 - 2076
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000276747600152
  • scopus:77950486591
ISSN
1527-3792
DOI
10.1016/j.juro.2009.12.093
language
English
LU publication?
yes
id
72c78c4c-2fd1-4602-a49d-0f575aa7b63d (old id 1602971)
date added to LUP
2010-05-19 10:05:11
date last changed
2018-05-29 10:34:09
@article{72c78c4c-2fd1-4602-a49d-0f575aa7b63d,
  abstract     = {Purpose: We studied whether TRPA1 agonists interact with sensory and inflammatory signals to relax human urethral smooth muscle. Materials and Methods: Urethral specimens were obtained perioperatively from 19 patients, and prepared for immunohistochemistry and functional experiments. The effects of allyl isothiocyanate, cinnamaldehyde and NaHS were studied in phenylephrine activated preparations combined with capsaicin, capsazepine, N omega-nitro-L-arginine, indomethacin or CP55940. Results: TRPA1, cannabinoid 1 and cannabinoid 2 immunoreactivity was colocalized in nerve fibers of the human urethra. All TRPA1 agonists produced relaxation of phenylephrine contracted urethral preparations. Capsaicin increased relaxant responses to all TRPA1 agonists. It increased the mean SEM -logIC50 of cinnamaldehyde and NaHS from 4.91 +/- 0.26 to 5.15 +/- 0.22 and 3.27 +/- 0.14 to 3.79 +/- 0.35, and the -logIC30 of allyl isothiocyanate from 3.11 +/- 0.24 to 3.41 +/- 0.26 (each p &lt; 0.05). Capsazepine in 5 preparations, indomethacin in 6 and CP55940 in 5 decreased cinnamaldehyde mediated relaxation by up to 39%, 88% and 89%, respectively. Nw-nitro-L-arginine and urothelial removal had no effect on relaxation by cinnamaldehyde in 5 preparations. Conclusions: Relaxation to TRPA1 agonists in human urethral preparations seem to work in cooperation with TRPV1 mediated signals, are negatively coupled via cannabinoid receptor activation and involve cyclooxygenase products. Urothelial TRPA1 signals may not be important to regulate normal human urethral smooth muscle tone. This does not exclude a role in the initiation of afferent activity normally and in disease states.},
  author       = {Weinhold, Philipp and Gratzke, Christian and Streng, Tomi and Stief, Christian and Andersson, Karl-Erik and Hedlund, Petter},
  issn         = {1527-3792},
  keyword      = {protein,human,TRPV1,TRPA1 protein,muscle relaxation,urethra,urothelium},
  language     = {eng},
  number       = {5},
  pages        = {2070--2076},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Urology},
  title        = {TRPA1 Receptor Induced Relaxation of the Human Urethra Involves TRPV1 and Cannabinoid Receptor Mediated Signals, and Cyclooxygenase Activation},
  url          = {http://dx.doi.org/10.1016/j.juro.2009.12.093},
  volume       = {183},
  year         = {2010},
}