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TRPA1 Channel 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 2771

Special Issue Editors

Department of Cellular Neurophysiology, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic
Interests: thermosensitive TRP channels; membrane biophysics; electrophysiology; nociception; mathematical modeling
Special Issues, Collections and Topics in MDPI journals
Department of Clinical Sciences Malmö, Lund University, SE-214 28 Malmö, Sweden
Interests: TRP channel chemosensitivity; TRP channel thermosensitivity; TRP channel mechanosensitivity; TRP secretory cell signaling; TRP pharmacology; nociception; pain
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The transient receptor potential ankyrin 1 receptor (TRPA1) is a cation channel expressed in dorsal root, trigeminal, and visceral primary sensory neurons, but also in various non-neuronal cells such as lung fibroblast and epithelial cells, smooth muscle cells, hair cells, keratinocytes, odontoblasts, astroglia, Schwann cells, and arterial vessels. There, TRPA1 acts as a multipurpose sensor of harmful signals, being activated by a wide range of chemical and physical stimuli. Accumulating evidence links the physiological functions of TRPA1 to nociception, inflammation, temperature perception, mechanosensation, insulin secretion, itching, respiratory functions, regulation of the cardiovascular system, and also the homeostatic balance between the immune and nociceptive systems. Given the wide expression pattern of TRPA1, a precise knowledge of the channel function is essential before it can be considered a potential target for the development of new, safe, and clinically relevant drugs.

Until very recently, information about the three-dimensional structure of TRPA1 has lagged behind information obtained from mutational and functional studies. At the break of 2019/2020, high-resolution structures of TRPA1 in different conformations have been published as a result of the recent “resolution revolution” in single-particle cryo-electron microscopy. Obviously, these new findings will further allow the rationalization of structure–activity studies, understanding the functional impact of TRPA1 genetic polymorphisms, and, perhaps more importantly, rational screening of novel modulators as potential selective therapeutic agents.

This Special Issue will provide a platform for original research papers and reviews describing the most recent findings in the TRPA1 field, covering any topics related to the biophysics, structure, pharmacology, physiological/pathophysiological roles, new molecular-based therapeutic strategies, and human genetic association studies.

Dr. Viktorie Vlachova
Prof. Peter M. Zygmunt
Guest Editors

Manuscript Submission Information

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Keywords

  • Transient receptor potential ankyrin subtype 1
  • Structure-function
  • Pain
  • Sensory neuron
  • Inflammation
  • Thermosensitive TRP channel
  • Mechanosensitive TRP channel

Published Papers (1 paper)

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Research

25 pages, 2973 KiB  
Article
The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO3 by the Porcine Colon
by David Manneck, Gisela Manz, Hannah-Sophie Braun, Julia Rosendahl and Friederike Stumpff
Int. J. Mol. Sci. 2021, 22(10), 5198; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105198 - 14 May 2021
Cited by 10 | Viewed by 2231
Abstract
A therapeutic potential of the TRPA1 channel agonist cinnamaldehyde for use in inflammatory bowel disease is emerging, but the mechanisms are unclear. Semi-quantitative qPCR of various parts of the porcine gastrointestinal tract showed that mRNA for TRPA1 was highest in the colonic mucosa. [...] Read more.
A therapeutic potential of the TRPA1 channel agonist cinnamaldehyde for use in inflammatory bowel disease is emerging, but the mechanisms are unclear. Semi-quantitative qPCR of various parts of the porcine gastrointestinal tract showed that mRNA for TRPA1 was highest in the colonic mucosa. In Ussing chambers, 1 mmol·L−1 cinnamaldehyde induced increases in short circuit current (ΔIsc) and conductance (ΔGt) across the colon that were higher than those across the jejunum or after 1 mmol·L−1 thymol. Lidocaine, amiloride or bumetanide did not change the response. The application of 1 mmol·L−1 quinidine or the bilateral replacement of 120 Na+, 120 Cl or 25 HCO3 reduced ΔGt, while the removal of Ca2+ enhanced ΔGt with ΔIsc numerically higher. ΔIsc decreased after 0.5 NPPB, 0.01 indometacin and the bilateral replacement of 120 Na+ or 25 HCO3. The removal of 120 Cl had no effect. Cinnamaldehyde also activates TRPV3, but comparative measurements involving patch clamp experiments on overexpressing cells demonstrated that much higher concentrations are required. We suggest that cinnamaldehyde stimulates the secretion of HCO3 via apical CFTR and basolateral Na+-HCO3 cotransport, preventing acidosis and damage to the epithelium and the colonic microbiome. Signaling may involve the opening of TRPA1, depolarization of the epithelium and a rise in PGE2 following a lower uptake of prostaglandins via OATP2A1. Full article
(This article belongs to the Special Issue TRPA1 Channel 2.0)
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