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Drugs Affecting TRP Channels

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 237))

Abstract

Chronic obstructive pulmonary disease (COPD) and asthma are both common respiratory diseases that are associated with airflow reduction/obstruction and pulmonary inflammation. Whilst drug therapies offer adequate symptom control for many mild to moderate asthmatic patients, severe asthmatics and COPD patients symptoms are often not controlled, and in these cases, irreversible structural damage occurs with disease progression over time. Transient receptor potential (TRP) channels, in particular TRPV1, TRPA1, TRPV4 and TRPM8, have been implicated with roles in the regulation of inflammation and autonomic nervous control of the lungs. Evidence suggests that inflammation elevates levels of activators and sensitisers of TRP channels and additionally that TRP channel expression may be increased, resulting in excessive channel activation. The enhanced activity of these channels is thought to then play a key role in the propagation and maintenance of the inflammatory disease state and neuronal symptoms such as bronchoconstriction and cough. For TRPM8 the evidence is less clear, but as with TRPV1, TRPA1 and TRPV4, antagonists are being developed by multiple companies for indications including asthma and COPD, which will help in elucidating their role in respiratory disease.

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References

  • Adcock JJ (2009) TRPV1 receptors in sensitisation of cough and pain reflexes. Pulm Pharmacol Ther 22:65–70

    Article  CAS  PubMed  Google Scholar 

  • Adcock JJ, Birrell MA, Maher SA et al (2014) Making sense of sensory nerves: an in vivo characterisation of Aδ- and C-fibres innervating Guinea-Pig Airways. Am J Respir Crit Care Med 189:A3969

    Google Scholar 

  • Akopian AN (2011) Regulation of nociceptive transmission at the periphery via TRPA1-TRPV1 interactions. Curr Pharm Biotechnol 12:89–94

    Article  CAS  PubMed  Google Scholar 

  • Alvarez DF, King JA, Weber D et al (2006) Transient receptor potential vanilloid 4-mediated disruption of the alveolar septal barrier: a novel mechanism of acute lung injury. Circ Res 99:988–995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andrè E, Campi B (2008) Cigarette smoke–induced neurogenic inflammation is mediated by α, β-unsaturated aldehydes and the TRPA1 receptor in rodents. J Clin Invest 118:2574–2582

    PubMed  PubMed Central  Google Scholar 

  • Andrè E, Gatti R, Trevisani M et al (2009) Transient receptor potential ankyrin receptor 1 is a novel target for protussive agents. Br J Pharmacol 158:1621–1628

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bandell M, Story GM, Hwang SW et al (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41:849–857

    Article  CAS  PubMed  Google Scholar 

  • Bang S, Hwang SW (2009) Polymodal ligand sensitivity of TRPA1 and its modes of interactions. J Gen Physiol 133:257–262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Banner KH, Igney F, Poll C (2011) TRP channels: emerging targets for respiratory disease. Pharmacol Ther 130:371–384

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ (2004) Mediators of chronic obstructive pulmonary disease. Pharmacol Rev 56:515–548

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ (2008) Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 8:183–192

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ (2013) Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol 131:636–645

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ, Stockley RA (2005) COPD: current therapeutic interventions and future approaches. Eur Respir J 25:1084–1106

    Article  CAS  PubMed  Google Scholar 

  • Bautista DM (2005) Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci 102:12248–12252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bautista DM, Pellegrino M, Tsunozaki M (2013) TRPA1: A gatekeeper for inflammation. Annu Rev Physiol 75:181–200

    Article  CAS  PubMed  Google Scholar 

  • Baxter M, Eltom S, Dekkak B et al (2014) Role of transient receptor potential and pannexin channels in cigarette smoke-triggered ATP release in the lung. Thorax 69:1080–1089

    Article  PubMed  Google Scholar 

  • Belmonte C, Viana F (2008) Molecular and cellular limits to somatosensory specificity. Mol Pain 4:14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Belvisi MG (2003) Sensory nerves and airway inflammation: role of Aδ and C-fibres. Pulm Pharmacol Ther 16:1–7

    Article  CAS  PubMed  Google Scholar 

  • Belvisi MG, Birrell MA, Khalid S et al (2016) Neurophenotypes in airway diseases. Insights from translational cough studies. Am J Resp Crit Care Med 193(12):1364–1372

    Article  PubMed  PubMed Central  Google Scholar 

  • Bessac BF, Sivula M, von Hehn CA et al (2008) TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest 118:1899–1910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Birrell MA, Belvisi MG, Grace M et al (2009) TRPA1 agonists evoke coughing in guinea pig and human volunteers. Am J Respir Crit Care Med 180:1042–1047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blanc F-X, Macedo P, Hew M, Chung KF (2009) Capsaicin cough sensitivity in smokers with and without airflow obstruction. Respir Med 103:786–790

    Article  PubMed  Google Scholar 

  • Bokesch PM, Chandorkar G, van Lier JJ, Donovan J (2012) Safety and pharmacokinetics (PK) of novel first-in-class analgesic: TRPA1 antagonist CB-189,625 in healthy adult males. In: 31st Annu. Eur. Soc. Reg. Anaesth. Congr.

    Google Scholar 

  • Bonney I, Carr D (2013) The future of pain pharmacotherapy. In: Deer TR, Leong MS, Buvanendran A, et al (eds) Comprehensive treatment of chronic pain by medical, interventional, and integrative approaches. Springer, New York, pp 199–209

    Google Scholar 

  • Bonvini SJ, Adcock JJ, Grace MS et al (2013) Activation of TRPV4 causes bronchoconstriction: a possible role in respiratory disease? Eur Respir J 42:1759

    Google Scholar 

  • Bonvini SJ, Birrell MA, Grace MS et al (2016) Transient receptor potential cation channel, subfamily V, member 4 and airway sensory afferent activation: role of adenosine triphosphate. J Allergy Clin Immunol 138:249–261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brierley SM, Castro J, Harrington AM et al (2011) TRPA1 contributes to specific mechanically activated currents and sensory neuron mechanical hypersensitivity. J Physiol 589:3575–3593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Büch TRH, Schäfer EAM, Demmel M-T et al (2013) Functional expression of the transient receptor potential channel TRPA1, a sensor for toxic lung inhalants, in pulmonary epithelial cells. Chem Biol Interact 206:462–471

    Article  PubMed  CAS  Google Scholar 

  • Buday T, Brozmanova M, Biringerova Z et al (2012) Modulation of cough response by sensory inputs from the nose – role of trigeminal TRPA1 versus TRPM8 channels. Cough 8:11

    Article  PubMed  PubMed Central  Google Scholar 

  • Caceres AI, Brackmann M, Elia MD et al (2009) A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Proc Natl Acad Sci 106:9099–9104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cantero-Recasens G, Gonzalez JR, Fandos C et al (2010) Loss of function of transient receptor potential vanilloid 1 (TRPV1) genetic variant is associated with lower risk of active childhood asthma. J Biol Chem 285:27532–27535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carlsen K-H, Carlsen KCL (2002) Exercise-induced asthma. Paediatr Respir Rev 3:154–160

    Article  PubMed  Google Scholar 

  • Caterina MJ, Schumacher MA, Tominaga M et al (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Joshi SK, DiDomenico S et al (2011) Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation. Pain 152:1165–1172

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Kang D, Xu J et al (2013) Species differences and molecular determinant of TRPA1 cold sensitivity. Nat Commun 4:2501

    PubMed  PubMed Central  Google Scholar 

  • Cho Y, Jang Y, Yang YD et al (2010) TRPM8 mediates cold and menthol allergies associated with mast cell activation. Cell Calcium 48:202–208

    Article  CAS  PubMed  Google Scholar 

  • Choudry NB, Fuller RW (1992) Sensitivity of the cough reflex in patients with chronic cough. Eur Respir J 5:296–300

    CAS  PubMed  Google Scholar 

  • Chung KF (2011) Chronic “cough hypersensitivity syndrome”: a more precise label for chronic cough. Pulm Pharmacol Ther 24:267–271

    Article  CAS  PubMed  Google Scholar 

  • Clapham DE (2005) International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacol Rev 57:427–450

    Article  CAS  PubMed  Google Scholar 

  • Clapham DE, Runnels LW, Strübing C (2001) The TRP ion channel family. Nat Rev Neurosci 2:387–396

    Article  CAS  PubMed  Google Scholar 

  • Coleridge JC, Coleridge HM (1984) Afferent vagal C fibre innervation of the lungs and airways and its functional significance. Rev Physiol Biochem Pharmacol 99:1–110

    CAS  PubMed  Google Scholar 

  • Couto M, de Diego A, Perpiñi M et al (2013) Cough reflex testing with inhaled capsaicin and TRPV1 activation in asthma and comorbid conditions. J Investig Allergol Clin Immunol 23:289–301

    CAS  PubMed  Google Scholar 

  • Cubist Pharmaceuticals (2013) Quarterly Report 31/03/13. In: OTC Mark. http://www.otcmarkets.com/edgar/GetFilingHtml?FilingID=9272339. Accessed 24 Nov 2014

  • D’hoedt D, Owsianik G, Prenen J et al (2008) Stimulus-specific modulation of the cation channel TRPV4 by PACSIN 3. J Biol Chem 283:6272–6280

    Article  PubMed  CAS  Google Scholar 

  • Decalmer SC, Webster D, Kelsall AA et al (2007) Chronic cough: how do cough reflex sensitivity and subjective assessments correlate with objective cough counts during ambulatory monitoring? Thorax 62:329–334

    Article  PubMed  Google Scholar 

  • Decramer M, Janssens W, Miravitlles M (2012) Chronic obstructive pulmonary disease. Lancet 379:1341–1351

    Article  PubMed  Google Scholar 

  • Delescluse I, Mace H, Adcock JJ (2012) Inhibition of airway hyper-responsiveness by TRPV1 antagonists (SB-705498 and PF-04065463) in the unanaesthetized, ovalbumin-sensitized guinea pig. Br J Pharmacol 166:1822–1832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dietrich A, Chubanov V, Kalwa H et al (2006) Cation channels of the transient receptor potential superfamily: their role in physiological and pathophysiological processes of smooth muscle cells. Pharmacol Ther 112:744–760

    Article  CAS  PubMed  Google Scholar 

  • Doherty MJ, Mister R, Pearson MG, Calverley PM (2000) Capsaicin responsiveness and cough in asthma and chronic obstructive pulmonary disease. Thorax 55:643–649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eccles R (2003) Menthol: effects on nasal sensation of airflow and the drive to breathe. Curr Allergy Asthma Rep 3:210–214

    Article  PubMed  Google Scholar 

  • Eder W, Ege MJ, von Mutius E (2006) The asthma epidemic. N Engl J Med 355:2226–2235

    Article  CAS  PubMed  Google Scholar 

  • Eltom S, Belvisi MG, Stevenson CS et al (2014) Role of the inflammasome-caspase1/11-IL-1/18 axis in cigarette smoke driven airway inflammation: an insight into the pathogenesis of COPD. PLoS One 9, e112829

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Esther CR, Alexis NE, Clas ML et al (2008) Extracellular purines are biomarkers of neutrophilic airway inflammation. Eur Respir J 31:949–956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Evaluate Group press release (2014) Glenmark’s TRPA1 antagonist “GRC 17536” shows positive data in a proof of concept study. http://www.evaluategroup.com/Universal/View.aspx?type=Story&id=530203. Accessed 15 Oct 2014

  • Everaerts W, Nilius B, Owsianik G (2010) The vanilloid transient receptor potential channel TRPV4: from structure to disease. Prog Biophys Mol Biol 103:2–17

    Article  CAS  PubMed  Google Scholar 

  • Ferrer-Montiel A, Fernández-Carvajal A, Planells-Cases R et al (2012) Advances in modulating thermosensory TRP channels. Expert Opin Ther Pat 22:999–1017

    Article  CAS  PubMed  Google Scholar 

  • Fischer MJM, Reeh PW (2007) Sensitization to heat through G-protein-coupled receptor pathways in the isolated sciatic mouse nerve. Eur J Neurosci 25:3570–3575

    Article  PubMed  Google Scholar 

  • Galeotti N, Di Cesare Mannelli L, Mazzanti G et al (2002) Menthol: a natural analgesic compound. Neurosci Lett 322:145–148

    Article  CAS  PubMed  Google Scholar 

  • Gavva NR, Treanor JJS, Garami A et al (2008) Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain 136:202–210

    Article  CAS  PubMed  Google Scholar 

  • Geppetti P, Patacchini R, Nassini R, Materazzi S (2009) Cough: the emerging role of the TRPA1 channel. Lung 188:63–68

    Article  CAS  Google Scholar 

  • Gharat L (2007) Medicinal chemistry of the vanilloid (Capsaicin) TRPV1 receptor: current knowledge and future perspectives. Drug Dev Res 68:477–497

    Article  CAS  Google Scholar 

  • Grace MS, Belvisi MG (2011) TRPA1 receptors in cough. Pulm Pharmacol Ther 24:286–288

    Article  CAS  PubMed  Google Scholar 

  • Grace M, Birrell MA, Dubuis E et al (2012) Transient receptor potential channels mediate the tussive response to prostaglandin E2 and bradykinin. Thorax 67:891–900

    Article  PubMed  PubMed Central  Google Scholar 

  • Grace MS, Baxter M, Dubuis E et al (2014) Transient receptor potential (TRP) channels in the airway: role in airway disease. Br J Pharmacol 171:2593–2607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grant AD, Cottrell GS, Amadesi S et al (2007) Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. J Physiol 578:715–733

    Article  CAS  PubMed  Google Scholar 

  • Groneberg DA (2004) Increased expression of transient receptor potential vanilloid-1 in airway nerves of chronic cough. Am J Respir Crit Care Med 170:1276–1280

    Article  PubMed  Google Scholar 

  • Hamanaka K, Jian M-Y, Townsley MI et al (2010) TRPV4 channels augment macrophage activation and ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 299:L353–L362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hargreave FE, Nair P (2009) The definition and diagnosis of asthma. Clin Allergy 39:1652–1658

    Article  CAS  Google Scholar 

  • Hinman A, Chuang H-H, Bautista DM, Julius D (2006) TRP channel activation by reversible covalent modification. Proc Natl Acad Sci U S A 103:19564–19568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hogg JC, Chu F, Utokaparch S et al (2004) The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 350:2645–2653

    Article  CAS  PubMed  Google Scholar 

  • Hondoh A, Ishida Y, Ugawa S et al (2010) Distinct expression of cold receptors (TRPM8 and TRPA1) in the rat nodose–petrosal ganglion complex. Brain Res 1319:60–69

    Article  CAS  PubMed  Google Scholar 

  • Hox V, Vanoirbeek JA, Alpizar YA et al (2013) Crucial role of transient receptor potential ankyrin 1 and mast cells in induction of nonallergic airway hyperreactivity in mice. Am J Respir Crit Care Med 187:486–493

    Article  CAS  PubMed  Google Scholar 

  • Ito S, Kume H, Shiraki A et al (2008) Inhibition by the cold receptor agonists menthol and icilin of airway smooth muscle contraction. Pulm Pharmacol Ther 21:812–817

    Article  CAS  PubMed  Google Scholar 

  • Jang Y, Lee Y, Kim SM et al (2012) Quantitative analysis of TRP channel genes in mouse organs. Arch Pharm Res 35:1823–1830

    Article  CAS  PubMed  Google Scholar 

  • Jaquemar D, Schenker T, Trueb B (1999) An ankyrin-like protein with transmembrane domains is specifically lost after oncogenic transformation of human fibroblasts. J Biol Chem 274:7325–7333

    Article  CAS  PubMed  Google Scholar 

  • Jia Y, Wang X, Varty L et al (2004) Functional TRPV4 channels are expressed in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 287:L272–L278

    Article  CAS  PubMed  Google Scholar 

  • Jian M-Y, King JA, Al-Mehdi AB et al (2008) High vascular pressure-induced lung injury requires P450 epoxygenase-dependent activation of TRPV4. Am J Respir Cell Mol Biol 38:386–392

    Article  CAS  PubMed  Google Scholar 

  • Jordt SE, Tominaga M, Julius D (2000) Acid potentiation of the capsaicin receptor determined by a key extracellular site. Proc Natl Acad Sci U S A 97:8134–8139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanezaki M, Ebihara S, Gui P et al (2012) Effect of cigarette smoking on cough reflex induced by TRPV1 and TRPA1 stimulations. Respir Med 106:406–412

    Article  PubMed  Google Scholar 

  • Karashima Y, Damann N, Prenen J et al (2007) Bimodal action of menthol on the transient receptor potential channel TRPA1. J Neurosci 27:9874–9884

    Article  CAS  PubMed  Google Scholar 

  • Kenia P, Houghton T, Beardsmore C (2008) Does inhaling menthol affect nasal patency or cough? Pediatr Pulmonol 43:532–537

    Article  PubMed  Google Scholar 

  • Khalid S, Murdoch R, Newlands A et al (2014) Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind randomized controlled trial. J Allergy Clin Immunol 134:56–62

    Article  CAS  PubMed  Google Scholar 

  • Kremeyer B, Lopera F, Cox JJ et al (2010) A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron 66:671–680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kym PR, Kort ME, Hutchins CW (2009) Analgesic potential of TRPV1 antagonists. Biochem Pharmacol 78:211–216

    Article  CAS  PubMed  Google Scholar 

  • Lai H, Rogers DF (2010) New pharmacotherapy for airway mucus hypersecretion in asthma and COPD: targeting intracellular signaling pathways. J Aerosol Med Pulm Drug Deliv 23:219–231

    Article  CAS  PubMed  Google Scholar 

  • Latorre R, Brauchi S, Orta G et al (2007) ThermoTRP channels as modular proteins with allosteric gating. Cell Calcium 42:427–438

    Article  CAS  PubMed  Google Scholar 

  • Latorre R, Brauchi S, Madrid R, Orio P (2011) A cool channel in cold transduction. Physiology (Bethesda) 26:273–285

    Article  CAS  Google Scholar 

  • Laude EA, Morice AH, Grattan TJ (1994) The antitussive effects of menthol, camphor and cineole in conscious guinea-pigs. Pulm Pharmacol 7:179–184

    Article  CAS  PubMed  Google Scholar 

  • Li M, Li Q, Yang G et al (2011) Cold temperature induces mucin hypersecretion from normal human bronchial epithelial cells in vitro through a transient receptor potential melastatin 8 (TRPM8)-mediated mechanism. J Allergy Clin Immunol 128:625–626

    Google Scholar 

  • Liedtke W, Choe Y, Martí-Renom MA et al (2000) Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell 103:525–535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lieu TM, Myers AC, Meeker S, Undem BJ (2012) TRPV1 induction in airway vagal low-threshold mechanosensory neurons by allergen challenge and neurotrophic factors. Am J Physiol Lung Cell Mol Physiol 302:L941–L948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lilly press release (2007) Lilly press release. https://investor.lilly.com/releasedetail.cfm?releaseid=271993

  • Lin YS, Hsu CC, Bien MY et al (2010) Activations of TRPA1 and P2X receptors are important in ROS-mediated stimulation of capsaicin-sensitive lung vagal afferents by cigarette smoke in rats. J Appl Physiol 108:1293–1303

    Article  CAS  PubMed  Google Scholar 

  • Lommatzsch M (2012) Airway hyperresponsiveness: new insights into the pathogenesis. Semin Respir Crit Care Med 33:579–587

    Article  PubMed  Google Scholar 

  • Macpherson LJ, Dubin AE, Evans MJ et al (2007) Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature 445:541–545

    Article  CAS  PubMed  Google Scholar 

  • Maher SA, Birrell MA, Belvisi MG (2009) Prostaglandin E2 mediates cough via the EP3 receptor: implications for future disease therapy. Am J Respir Crit Care Med 180:923–928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maher S, Birrell M, Bonvini S et al (2014) P6 Menthol has beneficial effects in the airways through a Trpm8-independent mechanism. Thorax 69:A79–A80

    Article  Google Scholar 

  • Malin S, Molliver D, Christianson JA et al (2011) TRPV1 and TRPA1 function and modulation are target tissue dependent. J Neurosci 31:10516–10528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Masoli M, Fabian D, Holt S et al (2004) The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 59:469–478

    Article  PubMed  Google Scholar 

  • McAlexander MA, Luttmann MA, Hunsberger GE, Undem BJ (2014) Transient receptor potential vanilloid 4 activation constricts the human bronchus via the release of cysteinyl leukotrienes. J Pharmacol Exp Ther 349:118–125

    Google Scholar 

  • McGarvey LP, Butler CA, Stokesberry S et al (2013) Increased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in patients with severe asthma. J Allergy Clin Immunol 133(3):704–12.e4

    Google Scholar 

  • McKemy DD (2013) The molecular and cellular basis of cold sensation. ACS Chem Neurosci 4:238–247

    Article  CAS  PubMed  Google Scholar 

  • Meseguer V, Alpizar YA, Luis E et al (2014) TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins. Nat Commun 5:3125

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Millqvist E (2011) The airway sensory hyperreactivity syndrome. Pulm Pharmacol Ther 24:263–266

    Article  CAS  PubMed  Google Scholar 

  • Millqvist E, Ternesten-Hasséus E, Bende M (2012) Inhalation of menthol reduces capsaicin cough sensitivity and influences inspiratory flows in chronic cough. Respir Med 107(3):433–438

    Article  PubMed  Google Scholar 

  • Mitchell JE, Campbell AP, New NE et al (2005) Expression and characterization of the intracellular vanilloid receptor (TRPV1) in bronchi from patients with chronic cough. Exp Lung Res 31:295–306

    Article  CAS  PubMed  Google Scholar 

  • Moparthi L, Survery S, Kreir M et al (2014) Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain. Proc Natl Acad Sci 111:16901–16906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moran MM, McAlexander MA, Bíró T, Szallasi A (2011) Transient receptor potential channels as therapeutic targets. Nat Rev Drug Discov 10:601–620

    Article  CAS  PubMed  Google Scholar 

  • Morice AH, Marshall AE, Higgins KS, Grattan TJ (1994) Effect of inhaled menthol on citric acid induced cough in normal subjects. Thorax 49:1024–1026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morosco G, Kiley J (2007) Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma–Summary Report 2007. J Allergy Clin Immunol 120:S94–S138

    Article  Google Scholar 

  • Mortaz E, Folkerts G, Nijkamp FP, Henricks PAJ (2010) ATP and the pathogenesis of COPD. Eur J Pharmacol 638:1–4

    Article  CAS  PubMed  Google Scholar 

  • Mukhopadhyay I, Gomes P, Aranake S et al (2011) Expression of functional TRPA1 receptor on human lung fibroblast and epithelial cells. J Recept Signal Transduct Res 31:350–358

    Article  CAS  PubMed  Google Scholar 

  • Mukhopadhyay I, Kulkarni A, Aranake S et al (2014) Transient receptor potential ankyrin 1 receptor activation in vitro and in vivo by pro-tussive agents: GRC 17536 as a promising anti-tussive therapeutic. PLoS One 9:e97005

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nash MS, McIntyre P, Groarke A et al (2012) 7-tert-Butyl-6-(4-chloro-phenyl)-2-thioxo-2,3-dihydro-1H-pyrido[2,3-d]pyrimidin-4-one, a classic polymodal inhibitor of transient receptor potential vanilloid type 1 with a reduced liability for hyperthermia, is analgesic and ameliorates visceral hypersensitivity. J Pharmacol Exp Ther 342:389–398

    Article  CAS  PubMed  Google Scholar 

  • Nassenstein C, Kwong K, Taylor-Clark T et al (2008) Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs. J Physiol 586:1595–1604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nassini R, Pedretti P, Moretto N et al (2012) Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. PLoS One 7:e42454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nilius B, Owsianik G (2010) Channelopathies converge on TRPV4. Nat Genet 42:98–100

    Article  CAS  PubMed  Google Scholar 

  • Nilius B, Szallasi A (2014) Transient receptor potential channels as drug targets: from the science of basic research to the art of medicine. Pharmacol Rev 66:676–814

    Article  PubMed  CAS  Google Scholar 

  • Nilius B, Voets T, Peters J (2005) TRP channels in disease. Sci STKE 2005:re8

    Google Scholar 

  • Nilius B, Appendino G, Owsianik G (2012) The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflugers Arch 464:425–458

    Article  CAS  PubMed  Google Scholar 

  • Okazawa M, Inoue W, Hori A et al (2004) Noxious heat receptors present in cold-sensory cells in rats. Neurosci Lett 359:33–36

    Article  CAS  PubMed  Google Scholar 

  • Paredi P, Goldman M, Alamen A et al (2010) Comparison of inspiratory and expiratory resistance and reactance in patients with asthma and chronic obstructive pulmonary disease. Thorax 65:263–267

    Article  PubMed  Google Scholar 

  • Peier AM, Moqrich A, Hergarden AC et al (2002) A TRP channel that senses cold stimuli and menthol. Cell 108:705–715

    Article  CAS  PubMed  Google Scholar 

  • Pharmeste website (2012) PHE377: A novel clinical-stage TRPV1 antagonist devoid of “class” side effects for the treatment of chronic pain syndromes. http://www.pharmeste.com/repository/contenuti/paragrafi/file/PharmEste_Leaflet_2012.pdf. Accessed 14 Nov 2014

  • Plevkova J, Kollarik M, Poliacek I et al (2013) The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol. J Appl Physiol 115:268–274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poole DP, Amadesi S, Veldhuis NA et al (2013) Protease-activated receptor 2 (PAR2) protein and transient receptor potential vanilloid 4 (TRPV4) protein coupling is required for sustained inflammatory signaling. J Biol Chem 288:5790–5802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prasad P, Yanagihara AA, Small-Howard AL et al (2008) Secretogranin III directs secretory vesicle biogenesis in mast cells in a manner dependent upon interaction with chromogranin A. J Immunol 181:5024–5034

    Article  CAS  PubMed  Google Scholar 

  • Preti D, Szallasi A, Patacchini R (2012) TRP channels as therapeutic targets in airway disorders: a patent review. Expert Opin Ther Pat 22:663–695

    Article  CAS  PubMed  Google Scholar 

  • Rabe KF, Hurd S, Anzueto A et al (2007) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 176:532–555

    Article  PubMed  Google Scholar 

  • Raemdonck K, de Alba J, Birrell MA et al (2012) A role for sensory nerves in the late asthmatic response. Thorax 67:19–25

    Article  PubMed  Google Scholar 

  • Rennard S, Decramer M, Calverley PMA et al (2002) Impact of COPD in North America and Europe in 2000: subjects’ perspective of Confronting COPD International Survey. Eur Respir J 20:799–805

    Article  CAS  PubMed  Google Scholar 

  • Riteau N, Gasse P, Fauconnier L et al (2010) Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am J Respir Crit Care Med 182:774–783

    Article  CAS  PubMed  Google Scholar 

  • Round P, Priestley A, Robinson J (2011) An investigation of the safety and pharmacokinetics of the novel TRPV1 antagonist XEN-D0501 in healthy subjects. Br J Clin Pharmacol 72:921–931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sabnis AS, Reilly CA, Veranth JM, Yost GS (2008a) Increased transcription of cytokine genes in human lung epithelial cells through activation of a TRPM8 variant by cold temperatures. Am J Physiol Lung Cell Mol Physiol 295:L194–L200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sabnis AS, Shadid M, Yost GS, Reilly CA (2008b) Human lung epithelial cells express a functional cold-sensing TRPM8 variant. Am J Respir Cell Mol Biol 39:466–474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sadofsky LR, Sreekrishna KT, Lin Y et al (2014) Unique responses are observed in transient receptor potential ankyrin 1 and vanilloid 1 (TRPA1 and TRPV1) co-expressing cells. Cells 3:616–626

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Salvi SS, Barnes PJ (2009) Chronic obstructive pulmonary disease in non-smokers. Lancet 374:733–743

    Article  PubMed  Google Scholar 

  • Seminario-Vidal L, Okada SF, Sesma JI et al (2011) Rho signaling regulates pannexin 1-mediated ATP release from airway epithelia. J Biol Chem 286:26277–26286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shapiro D, Deering-Rice CE, Romero EG et al (2013) Activation of transient receptor potential ankyrin-1 (TRPA1) in lung cells by wood smoke particulate material. Chem Res Toxicol 26:750–758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simon SA, Liedtke W (2008) How irritating: the role of TRPA1 in sensing cigarette smoke and aerogenic oxidants in the airways. J Clin Invest 118:2383–2386

    CAS  PubMed  PubMed Central  Google Scholar 

  • Smit LAM, Kogevinas M, Antó JM et al (2012) Transient receptor potential genes, smoking, occupational exposures and cough in adults. Respir Res 13:26

    Article  PubMed  PubMed Central  Google Scholar 

  • Story GM, Peier AM, Reeve AJ et al (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112:819–829

    Article  CAS  PubMed  Google Scholar 

  • Sturton G, Persson C, Barnes PJ (2008) Small airways: an important but neglected target in the treatment of obstructive airway diseases. Trends Pharmacol Sci 29:340–345

    Article  CAS  PubMed  Google Scholar 

  • Sumner H, Woodcock A, Kolsum U et al (2013) Predictors of objective cough frequency in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 187(9):943–949

    Article  PubMed  Google Scholar 

  • Szallasi A, Cortright DN, Blum CA, Eid SR (2007) The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept. Nat Rev Drug Discov 6:357–372

    Article  CAS  PubMed  Google Scholar 

  • Szolcsányi J, Sándor Z (2012) Multisteric TRPV1 nocisensor: a target for analgesics. Trends Pharmacol Sci 33:646–655

    Article  PubMed  CAS  Google Scholar 

  • Takahara N, Ito S, Furuya K et al (2014) Real-time imaging of ATP release induced by mechanical stretch in human airway smooth muscle cells. Am J Respir Cell Mol Biol 51(6):772–782

    Article  PubMed  CAS  Google Scholar 

  • Taylor-Clark TE, Undem BJ, MacGlashan DW et al (2007) Prostaglandin-induced activation of nociceptive neurons via direct interaction with transient receptor potential A1 (TRPA1). Mol Pharmacol 73:274–281

    Article  PubMed  CAS  Google Scholar 

  • Taylor-Clark TE, McAlexander MA, Nassenstein C et al (2008) Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C-fibres by the endogenous autacoid 4-oxononenal. J Physiol 586:3447–3459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thorneloe KS, Cheung M, Bao W et al (2012) An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Transl Med 4:159ra148

    Google Scholar 

  • Tränkner D, Hahne N, Sugino K et al (2014) Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways. Proc Natl Acad Sci 111:11515–11520

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Trevisani M, Siemens J, Materazzi S et al (2007) 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci 104:13519–13524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Veldhuis NA, Poole DP, Grace M et al (2015) The G protein-coupled receptor-transient receptor potential channel axis: molecular insights for targeting disorders of sensation and inflammation. Pharmacol Rev 67:36–73

    Article  PubMed  CAS  Google Scholar 

  • Vennekens R, Owsianik G, Nilius B (2008) Vanilloid transient receptor potential cation channels: an overview. Curr Pharm Des 14:18–31

    Article  CAS  PubMed  Google Scholar 

  • Vergnolle N, Cenac N, Altier C et al (2010) A role for transient receptor potential vanilloid 4 in tonicity-induced neurogenic inflammation. Br J Pharmacol 159:1161–1173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vestbo J, Hurd SS, Agustí AG et al (2013) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 187:347–365

    Article  CAS  PubMed  Google Scholar 

  • Vincent F, Duncton MAJ (2011) TRPV4 agonists and antagonists. Curr Top Med Chem 11:2216–2226

    Article  CAS  PubMed  Google Scholar 

  • Vriens J, Watanabe H, Janssens A et al (2004) Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4. Proc Natl Acad Sci U S A 101:396–401

    Article  CAS  PubMed  Google Scholar 

  • Vriens J, Owsianik G, Janssens A et al (2007) Determinants of 4 alpha-phorbol sensitivity in transmembrane domains 3 and 4 of the cation channel TRPV4. J Biol Chem 282:12796–12803

    Article  CAS  PubMed  Google Scholar 

  • Vriens J, Appendino G, Nilius B (2009) Pharmacology of vanilloid transient receptor potential cation channels. Mol Pharmacol 75:1262–1279

    Article  CAS  PubMed  Google Scholar 

  • Watanabe H, Vriens J, Prenen J (2003) Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 424:434–438

    Article  CAS  PubMed  Google Scholar 

  • Weinfeld D, Ternesten-Hasséus E, Löwhagen O, Millqvist E (2002) Capsaicin cough sensitivity in allergic asthmatic patients increases during the birch pollen season. Ann Allergy Asthma Immunol 89:419–424

    Article  PubMed  Google Scholar 

  • Willart MAM, Lambrecht BN (2009) The danger within: endogenous danger signals, atopy and asthma. Clin Exp Allergy 39:12–19

    Article  CAS  PubMed  Google Scholar 

  • Willette RN, Bao W, Nerurkar S et al (2008) Systemic activation of the transient receptor potential vanilloid subtype 4 channel causes endothelial failure and circulatory collapse: Part 2. J Pharmacol Exp Ther 326:443–452

    Article  CAS  PubMed  Google Scholar 

  • Willis DN, Liu B, Ha MA et al (2011) Menthol attenuates respiratory irritation responses to multiple cigarette smoke irritants. FASEB J 25:4434–4444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winchester W, Gore K, Glatt S (2014) Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans. J Pharmacol Exp Ther 351:259–269

    Article  PubMed  CAS  Google Scholar 

  • Wise PM, Breslin PAS, Dalton P (2012) Sweet taste and menthol increase cough reflex thresholds. Pulm Pharmacol Ther 25:236–241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong CH, Morice AH (1999) Cough threshold in patients with chronic obstructive pulmonary disease. Thorax 54:62–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wortley M, Maher S, Bonvini S et al (2014a) P4 establishing a role for Trpv1 on sensory nerves in Copd associated chronic cough. Thorax 69:A78–A79

    Google Scholar 

  • Wortley MA, Birrell MA, Maher SA et al (2014b) Profiling of XEN-D0501, a novel TRPV1 antagonist, in pre-clinical models of cough. Am J Respir Crit Care Med American Thoracic Society, A4979

    Google Scholar 

  • Wright CE, Laude EA, Grattan TJ, Morice AH (1997) Capsaicin and neurokinin A-induced bronchoconstriction in the anaesthetised guinea-pig: evidence for a direct action of menthol on isolated bronchial smooth muscle. Br J Pharmacol 121:1645–1650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu L-J, Sweet T-B, Clapham DE (2010) International Union of Basic and Clinical Pharmacology. LXXVI. Current progress in the mammalian TRP ion channel family. Pharmacol Rev 62:381–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xia R, Dekermendjian K, Lullau E, Dekker N (2011) TRPV1: a therapy target that attracts the pharmaceutical interests. Adv Exp Med Biol 704:637–665

    Article  CAS  PubMed  Google Scholar 

  • Xing H, Ling JX, Chen M et al (2008) TRPM8 mechanism of autonomic nerve response to cold in respiratory airway. Mol Pain 4:22

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang X-R (2006) Functional expression of transient receptor potential melastatin- and vanilloid-related channels in pulmonary arterial and aortic smooth muscle. Am J Physiol Lung Cell Mol Physiol 290:L1267–L1276

    Article  CAS  PubMed  Google Scholar 

  • Yoshihara S, Geppetti P, Hara M et al (1996) Cold air-induced bronchoconstriction is mediated by tachykinin and kinin release in guinea pigs. Eur J Pharmacol 296:291–296

    Article  CAS  PubMed  Google Scholar 

  • Young EC, Brammer C, Owen E et al (2009) The effect of mindfulness meditation on cough reflex sensitivity. Thorax 64:993–998

    Article  CAS  PubMed  Google Scholar 

  • Zhang G, Lin RL, Wiggers M et al (2008) Altered expression of TRPV1 and sensitivity to capsaicin in pulmonary myelinated afferents following chronic airway inflammation in the rat. J Physiol 586:5771–5786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Sun B, Li Q et al (2011) Sensitivity of bronchopulmonary receptors to cold and heat mediated by transient receptor potential cation channel subtypes in an ex vivo rat lung preparation. Respir Physiol Neurobiol 177:327–332

    Article  CAS  PubMed  Google Scholar 

  • Zhu G, Gulsvik A, Bakke P et al (2009) Association of TRPV4 gene polymorphisms with chronic obstructive pulmonary disease. Hum Mol Genet 18:2053–2062

    Article  CAS  PubMed  Google Scholar 

  • Zygmunt PM, Petersson J, Andersson DA et al (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400:452–457

    Article  CAS  PubMed  Google Scholar 

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Wortley, M.A., Birrell, M.A., Belvisi, M.G. (2016). Drugs Affecting TRP Channels. In: Page, C., Barnes, P. (eds) Pharmacology and Therapeutics of Asthma and COPD. Handbook of Experimental Pharmacology, vol 237. Springer, Cham. https://doi.org/10.1007/164_2016_63

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