The transient receptor potential A1 ion channel (TRPA1) modifies in vivo autonomous ureter peristalsis in rats
(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.
(Less)
- author
- Weinhold, Philipp ; Villa, Luca ; Strittmatter, Frank ; Gratzke, Christian ; Stief, Christian G. ; Castiglione, Fabio ; Montorsi, Francesco and Hedlund, Petter LU
- organization
- publishing date
- 2021
- 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
-
- pmid:33232544
- scopus:85096707985
- 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
- 2024-08-08 07:12:41
@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 < 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.</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}}, }