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The transient receptor potential A1 ion channel (TRPA1) modifies in vivo autonomous ureter peristalsis in rats

Weinhold, Philipp ; Villa, Luca ; Strittmatter, Frank ; Gratzke, Christian ; Stief, Christian G. ; Castiglione, Fabio ; Montorsi, Francesco and Hedlund, Petter LU (2021) In Neurourology and Urodynamics 40(1). p.147-157
Abstract

Aims: The current study aimed to explore the expression of transient receptor potential A1 ion channels (TRPA1) in the rat ureter and to assess if TRPA1-active compounds modulate ureter function. Methods: The expression of TRPA1 in rat ureter tissue was studied by immunofluorescence. The TRPA1 distribution was compared to calcitonin gene-related peptide (CGRP), α-actin (SMA1), anoctamin-1 (ANO1), and c-kit. For in vivo analyses, a catheter was implanted in the right ureter of 50 rats. Ureter peristalsis and pressures were continuously recorded by a data acquisition set-up during intraluminal infusion of saline (baseline), saline plus protamine sulfate (PS; to disrupt the urothelium), saline plus PS with hydrogen sulfide (NaHS) or... (More)

Aims: The current study aimed to explore the expression of transient receptor potential A1 ion channels (TRPA1) in the rat ureter and to assess if TRPA1-active compounds modulate ureter function. Methods: The expression of TRPA1 in rat ureter tissue was studied by immunofluorescence. The TRPA1 distribution was compared to calcitonin gene-related peptide (CGRP), α-actin (SMA1), anoctamin-1 (ANO1), and c-kit. For in vivo analyses, a catheter was implanted in the right ureter of 50 rats. Ureter peristalsis and pressures were continuously recorded by a data acquisition set-up during intraluminal infusion of saline (baseline), saline plus protamine sulfate (PS; to disrupt the urothelium), saline plus PS with hydrogen sulfide (NaHS) or cinnamaldehyde (CA). Comparisons were made between rats treated systemically with vehicle or a TRPA1-antagonist (HC030031). Results: TRPA1-immunoreactive nerves co-expressed CGRP and were mainly located in the suburothelial region of the ureter. Immunoreactivity for TRPA1 was also encountered in c-kit-positive but ANO1-negative cells of the ureter suburothelium and wall. In vivo, HC030031-treated rats had elevated baseline peristaltic frequency (p < 0.05) and higher intraluminal pressures (p < 0.01). PS increased the frequency of ureter peristalsis versus baseline in vehicle-treated rats (p < 0.001) but not in HC030031-treated rats. CA (p < 0.001) and NaHS (p < 0.001) decreased ureter peristalsis. This was counteracted by HC030031 (p < 0.05 and p < 0.01). Conclusions: In rats, TRPA1 is expressed on cellular structures considered of importance for peristaltic and mechanoafferent functions of the ureter. Functional data indicate that TRPA1-mediated signals regulate ureter peristalsis. This effect was pronounced after mucosal disruption and suggests a role for TRPA1 in ureter pathologies involving urothelial damage.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ankyrin 1, cinnamaldehyde, HS, interstitial cell, nerve, pacing
in
Neurourology and Urodynamics
volume
40
issue
1
pages
147 - 157
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85096707985
  • pmid:33232544
ISSN
0733-2467
DOI
10.1002/nau.24579
language
English
LU publication?
yes
id
64e73188-c483-40c3-a406-7580d99b6511
date added to LUP
2020-12-09 07:58:54
date last changed
2024-05-30 01:27:03
@article{64e73188-c483-40c3-a406-7580d99b6511,
  abstract     = {{<p>Aims: The current study aimed to explore the expression of transient receptor potential A1 ion channels (TRPA1) in the rat ureter and to assess if TRPA1-active compounds modulate ureter function. Methods: The expression of TRPA1 in rat ureter tissue was studied by immunofluorescence. The TRPA1 distribution was compared to calcitonin gene-related peptide (CGRP), α-actin (SMA1), anoctamin-1 (ANO1), and c-kit. For in vivo analyses, a catheter was implanted in the right ureter of 50 rats. Ureter peristalsis and pressures were continuously recorded by a data acquisition set-up during intraluminal infusion of saline (baseline), saline plus protamine sulfate (PS; to disrupt the urothelium), saline plus PS with hydrogen sulfide (NaHS) or cinnamaldehyde (CA). Comparisons were made between rats treated systemically with vehicle or a TRPA1-antagonist (HC030031). Results: TRPA1-immunoreactive nerves co-expressed CGRP and were mainly located in the suburothelial region of the ureter. Immunoreactivity for TRPA1 was also encountered in c-kit-positive but ANO1-negative cells of the ureter suburothelium and wall. In vivo, HC030031-treated rats had elevated baseline peristaltic frequency (p &lt; 0.05) and higher intraluminal pressures (p &lt; 0.01). PS increased the frequency of ureter peristalsis versus baseline in vehicle-treated rats (p &lt; 0.001) but not in HC030031-treated rats. CA (p &lt; 0.001) and NaHS (p &lt; 0.001) decreased ureter peristalsis. This was counteracted by HC030031 (p &lt; 0.05 and p &lt; 0.01). Conclusions: In rats, TRPA1 is expressed on cellular structures considered of importance for peristaltic and mechanoafferent functions of the ureter. Functional data indicate that TRPA1-mediated signals regulate ureter peristalsis. This effect was pronounced after mucosal disruption and suggests a role for TRPA1 in ureter pathologies involving urothelial damage.</p>}},
  author       = {{Weinhold, Philipp and Villa, Luca and Strittmatter, Frank and Gratzke, Christian and Stief, Christian G. and Castiglione, Fabio and Montorsi, Francesco and Hedlund, Petter}},
  issn         = {{0733-2467}},
  keywords     = {{ankyrin 1; cinnamaldehyde; HS; interstitial cell; nerve; pacing}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{147--157}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Neurourology and Urodynamics}},
  title        = {{The transient receptor potential A1 ion channel (TRPA1) modifies in vivo autonomous ureter peristalsis in rats}},
  url          = {{http://dx.doi.org/10.1002/nau.24579}},
  doi          = {{10.1002/nau.24579}},
  volume       = {{40}},
  year         = {{2021}},
}