Transient receptor potential a1 (TRPA1) agonists inhibit contractions of the isolated human ureter
(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
- Weinhold, Philipp ; Hennenberg, Martin ; Strittmatter, Frank ; Stief, Christian G. ; Gratzke, Christian and Hedlund, Petter LU
- organization
- publishing date
- 2018-02-01
- 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 Inc.
- external identifiers
-
- scopus:85021705863
- pmid:28671709
- 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
- 2025-04-04 14:36:29
@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 < 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}},
keywords = {{ankyrin 1 nerve; cinnamaldehyde; contraction; H2S; interstitial cell; isothiocyanate; TRPV1}},
language = {{eng}},
month = {{02}},
number = {{2}},
pages = {{600--608}},
publisher = {{John Wiley & Sons Inc.}},
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}},
doi = {{10.1002/nau.23338}},
volume = {{37}},
year = {{2018}},
}