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The transient receptor potential A1 ion channel (TRPA1) modifies in vivo autonomous ureter peristalsis in rats
Author(s) -
Weinhold Philipp,
Villa Luca,
Strittmatter Frank,
Gratzke Christian,
Stief Christian G.,
Castiglione Fabio,
Montorsi Francesco,
Hedlund Petter
Publication year - 2021
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.24579
Subject(s) - peristalsis , ureter , medicine , calcitonin gene related peptide , endocrinology , in vivo , transient receptor potential channel , saline , receptor , urology , biology , neuropeptide , microbiology and biotechnology
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.