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Pharmaceuticals 2016, 9(4), 70; doi:10.3390/ph9040070

Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise?

Biological Research, Glenmark Research Centre, Glenmark Pharmaceuticals Ltd. Navi Mumbai, Maharashtra 400709, India
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Author to whom correspondence should be addressed.
Academic Editors: Arpad Szallasi and Jean Jacques Vanden Eynde
Received: 14 July 2016 / Revised: 23 September 2016 / Accepted: 28 September 2016 / Published: 5 November 2016
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Abstract

Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of “chemosensor”, detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and cystic fibrosis. TRPA1 can remain activated chronically due to elevated levels and continued presence of such endogenous ligands and pro-inflammatory mediators. Several selective TRPA1 antagonists have been tested in animal models of respiratory disease and their performance is very promising. Although there is no TRPA1 antagonist in advanced clinical trials or approved on market yet to treat respiratory diseases, however, limited but promising evidences available so far indicate likelihood that targeting TRPA1 may present a new therapy in treatment of respiratory diseases in near future. This review will focus on in vitro, animal and human evidences that strengthen the proposed role of TRPA1 in modulation of specific airway sensory responses and also on preclinical and clinical progress of selected TRPA1 antagonists. View Full-Text
Keywords: TRPA1; airway inflammation; airway sensory responses; asthma; COPD; cough TRPA1; airway inflammation; airway sensory responses; asthma; COPD; cough
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Mukhopadhyay, I.; Kulkarni, A.; Khairatkar-Joshi, N. Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise? Pharmaceuticals 2016, 9, 70.

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