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      The emerging role of transient receptor potential channels in chronic lung disease

      research-article
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      The European Respiratory Journal
      European Respiratory Society

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          Abstract

          Chronic lung diseases such as asthma, chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis are a major and increasing global health burden with a high unmet need. Drug discovery efforts in this area have been largely disappointing and so new therapeutic targets are needed. Transient receptor potential ion channels are emerging as possible therapeutic targets, given their widespread expression in the lung, their role in the modulation of inflammatory and structural changes and in the production of respiratory symptoms, such as bronchospasm and cough, seen in chronic lung disease.

          Abstract

          Transient receptor potential channels are emerging as novel targets for chronic lung diseases with a high unmet need http://ow.ly/GHeR30b3hIy

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          Most cited references124

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          TRP channels as cellular sensors.

          TRP channels are the vanguard of our sensory systems, responding to temperature, touch, pain, osmolarity, pheromones, taste and other stimuli. But their role is much broader than classical sensory transduction. They are an ancient sensory apparatus for the cell, not just the multicellular organism, and they have been adapted to respond to all manner of stimuli, from both within and outside the cell.
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            TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents.

            TRPA1 is an excitatory ion channel targeted by pungent irritants from mustard and garlic. TRPA1 has been proposed to function in diverse sensory processes, including thermal (cold) nociception, hearing, and inflammatory pain. Using TRPA1-deficient mice, we now show that this channel is the sole target through which mustard oil and garlic activate primary afferent nociceptors to produce inflammatory pain. TRPA1 is also targeted by environmental irritants, such as acrolein, that account for toxic and inflammatory actions of tear gas, vehicle exhaust, and metabolic byproducts of chemotherapeutic agents. TRPA1-deficient mice display normal cold sensitivity and unimpaired auditory function, suggesting that this channel is not required for the initial detection of noxious cold or sound. However, TRPA1-deficient mice exhibit pronounced deficits in bradykinin-evoked nociceptor excitation and pain hypersensitivity. Thus, TRPA1 is an important component of the transduction machinery through which environmental irritants and endogenous proalgesic agents depolarize nociceptors to elicit inflammatory pain.
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              A TRP channel that senses cold stimuli and menthol.

              A distinct subset of sensory neurons are thought to directly sense changes in thermal energy through their termini in the skin. Very little is known about the molecules that mediate thermoreception by these neurons. Vanilloid Receptor 1 (VR1), a member of the TRP family of channels, is activated by noxious heat. Here we describe the cloning and characterization of TRPM8, a distant relative of VR1. TRPM8 is specifically expressed in a subset of pain- and temperature-sensing neurons. Cells overexpressing the TRPM8 channel can be activated by cold temperatures and by a cooling agent, menthol. Our identification of a cold-sensing TRP channel in a distinct subpopulation of sensory neurons implicates an expanded role for this family of ion channels in somatic sensory detection.
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                Author and article information

                Journal
                Eur Respir J
                Eur. Respir. J
                ERJ
                erj
                The European Respiratory Journal
                European Respiratory Society
                0903-1936
                1399-3003
                August 2017
                03 August 2017
                : 50
                : 2
                : 1601357
                Affiliations
                Respiratory Pharmacology Group, Airway Disease Section, National Heart and Lung Institute, Imperial College, London, UK
                Author notes
                Maria G. Belvisi, Respiratory Pharmacology Group, Airway Disease Section, National Heart and Lung Institute, Imperial College, Exhibition Road, London SW7 2AZ, UK. E-mail: m.belvisi@ 123456imperial.ac.uk
                Article
                ERJ-01357-2016
                10.1183/13993003.01357-2016
                5593401
                28775042
                14ae0055-bd74-4c64-bbe5-e05845c8366f
                Copyright ©ERS 2017
                History
                : 08 January 2017
                : 14 April 2017
                Categories
                Back to Basics

                Respiratory medicine
                Respiratory medicine

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