Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise?
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 duct...
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| Format: | Article |
| Language: | English |
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MDPI AG
2016-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | http://www.mdpi.com/1424-8247/9/4/70 |
| _version_ | 1818339224935464960 |
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| author | Indranil Mukhopadhyay Abhay Kulkarni Neelima Khairatkar-Joshi |
| author_facet | Indranil Mukhopadhyay Abhay Kulkarni Neelima Khairatkar-Joshi |
| author_sort | Indranil Mukhopadhyay |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T15:23:37Z |
| format | Article |
| id | doaj.art-716af792030946218a5d0a60d752f568 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-12-13T15:23:37Z |
| publishDate | 2016-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-716af792030946218a5d0a60d752f5682022-12-21T23:40:27ZengMDPI AGPharmaceuticals1424-82472016-11-01947010.3390/ph9040070ph9040070Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise?Indranil Mukhopadhyay0Abhay Kulkarni1Neelima Khairatkar-Joshi2Biological Research, Glenmark Research Centre, Glenmark Pharmaceuticals Ltd. Navi Mumbai, Maharashtra 400709, IndiaBiological Research, Glenmark Research Centre, Glenmark Pharmaceuticals Ltd. Navi Mumbai, Maharashtra 400709, IndiaBiological Research, Glenmark Research Centre, Glenmark Pharmaceuticals Ltd. Navi Mumbai, Maharashtra 400709, IndiaTransient 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.http://www.mdpi.com/1424-8247/9/4/70TRPA1airway inflammationairway sensory responsesasthmaCOPDcough |
| spellingShingle | Indranil Mukhopadhyay Abhay Kulkarni Neelima Khairatkar-Joshi Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise? Pharmaceuticals TRPA1 airway inflammation airway sensory responses asthma COPD cough |
| title | Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise? |
| title_full | Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise? |
| title_fullStr | Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise? |
| title_full_unstemmed | Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise? |
| title_short | Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise? |
| title_sort | blocking trpa1 in respiratory disorders does it hold a promise |
| topic | TRPA1 airway inflammation airway sensory responses asthma COPD cough |
| url | http://www.mdpi.com/1424-8247/9/4/70 |
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