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Transient receptor potential a1 (TRPA1) agonists inhibit contractions of the isolated human ureter

Weinhold, Philipp; Hennenberg, Martin; Strittmatter, Frank; Stief, Christian G.; Gratzke, Christian and Hedlund, Petter LU (2018) In Neurourology and Urodynamics 37(2). p.600-608
Abstract

Aims: Mechanoafferent and peristaltic mechanisms of the human ureter involve transient receptor potential V1 (TRPV1)- and purinoceptor-mediated functions. Hydrogen sulphide, an endogenous TRPA1 ligand, is linked to inhibitory neurotransmission of the pig ureter. No information is available on TRPA1 activity in the human ureter. We therefore examined the distribution and function of TRPA1 in the human ureter. Methods: Expression of TRPA1 in human ureter tissue was studied by Western blot and immunofluorescence. The TRPA1 distribution was compared to TRPV1, calcitonin gene related peptide (CGRP), tyrosine hydroxylase (TH), and vimentin. Effects of the TRPA1 agonists allyl isothiocyanate (AI), cinnamaldehyde (CA), sodium hydrogen sulfide... (More)

Aims: Mechanoafferent and peristaltic mechanisms of the human ureter involve transient receptor potential V1 (TRPV1)- and purinoceptor-mediated functions. Hydrogen sulphide, an endogenous TRPA1 ligand, is linked to inhibitory neurotransmission of the pig ureter. No information is available on TRPA1 activity in the human ureter. We therefore examined the distribution and function of TRPA1 in the human ureter. Methods: Expression of TRPA1 in human ureter tissue was studied by Western blot and immunofluorescence. The TRPA1 distribution was compared to TRPV1, calcitonin gene related peptide (CGRP), tyrosine hydroxylase (TH), and vimentin. Effects of the TRPA1 agonists allyl isothiocyanate (AI), cinnamaldehyde (CA), sodium hydrogen sulfide (NaHS), and capsaicin (TRPV1 agonist) on human ureter preparations were studied in organ baths. Results: By Western blot, bands were detected at the expected molecular weight for TRPA1. TRPA1- and TRPV1-immunoreactivities were located on CGRP-positive nerves, but not on TH-positive nerves. TRPA1 was also located in vimentin-positive interstitial cells. In functional experiments, neither of the TRPA1-agonists (1-100 μM) had any direct effects on ureter tension (baseline/potassium-induced contractions). However, CA, AI, NaHS, and capsaicin (10 μM) decreased (P < 0.01-0.05) tetrodotoxin-sensitive electrically induced (2,4,8,16,32 Hz) contractions. Inhibitory activities were 50-61% (CA), 30-56% (AI), 30-40% (NaHS), and 37-67% (Capsaicin). Conclusions: In the human ureter, TRPA1 is located to sensory nerves and interstitial cells. TRPA1 agonists inhibited electrically induced contractions but had no direct effect on smooth muscle tension of the human ureter. A role for TRPA1 in modulating neurotransmission and possibly peristalsis of the human ureter is proposed.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
ankyrin 1 nerve, cinnamaldehyde, contraction, H2S, interstitial cell, isothiocyanate, TRPV1
in
Neurourology and Urodynamics
volume
37
issue
2
pages
9 pages
publisher
John Wiley & Sons
external identifiers
  • scopus:85021705863
ISSN
0733-2467
DOI
10.1002/nau.23338
language
English
LU publication?
yes
id
3a38dd79-74d5-419d-9589-3d92829fc997
date added to LUP
2018-05-22 07:41:23
date last changed
2019-08-14 04:16:44
@article{3a38dd79-74d5-419d-9589-3d92829fc997,
  abstract     = {<p>Aims: Mechanoafferent and peristaltic mechanisms of the human ureter involve transient receptor potential V1 (TRPV1)- and purinoceptor-mediated functions. Hydrogen sulphide, an endogenous TRPA1 ligand, is linked to inhibitory neurotransmission of the pig ureter. No information is available on TRPA1 activity in the human ureter. We therefore examined the distribution and function of TRPA1 in the human ureter. Methods: Expression of TRPA1 in human ureter tissue was studied by Western blot and immunofluorescence. The TRPA1 distribution was compared to TRPV1, calcitonin gene related peptide (CGRP), tyrosine hydroxylase (TH), and vimentin. Effects of the TRPA1 agonists allyl isothiocyanate (AI), cinnamaldehyde (CA), sodium hydrogen sulfide (NaHS), and capsaicin (TRPV1 agonist) on human ureter preparations were studied in organ baths. Results: By Western blot, bands were detected at the expected molecular weight for TRPA1. TRPA1- and TRPV1-immunoreactivities were located on CGRP-positive nerves, but not on TH-positive nerves. TRPA1 was also located in vimentin-positive interstitial cells. In functional experiments, neither of the TRPA1-agonists (1-100 μM) had any direct effects on ureter tension (baseline/potassium-induced contractions). However, CA, AI, NaHS, and capsaicin (10 μM) decreased (P &lt; 0.01-0.05) tetrodotoxin-sensitive electrically induced (2,4,8,16,32 Hz) contractions. Inhibitory activities were 50-61% (CA), 30-56% (AI), 30-40% (NaHS), and 37-67% (Capsaicin). Conclusions: In the human ureter, TRPA1 is located to sensory nerves and interstitial cells. TRPA1 agonists inhibited electrically induced contractions but had no direct effect on smooth muscle tension of the human ureter. A role for TRPA1 in modulating neurotransmission and possibly peristalsis of the human ureter is proposed.</p>},
  author       = {Weinhold, Philipp and Hennenberg, Martin and Strittmatter, Frank and Stief, Christian G. and Gratzke, Christian and Hedlund, Petter},
  issn         = {0733-2467},
  keyword      = {ankyrin 1 nerve,cinnamaldehyde,contraction,H2S,interstitial cell,isothiocyanate,TRPV1},
  language     = {eng},
  month        = {02},
  number       = {2},
  pages        = {600--608},
  publisher    = {John Wiley & Sons},
  series       = {Neurourology and Urodynamics},
  title        = {Transient receptor potential a1 (TRPA1) agonists inhibit contractions of the isolated human ureter},
  url          = {http://dx.doi.org/10.1002/nau.23338},
  volume       = {37},
  year         = {2018},
}