Skip to main content
SpringerLink
Log in

Chemosensory TRP Channels in the Respiratory Tract: Role in Toxic Lung Injury and Potential as “Sweet Spots” for Targeted Therapies

  • Chapter
  • First Online:
Reviews of Physiology, Biochemistry and Pharmacology, Vol. 165

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 165))

Abstract

Acute toxic lung injury by reactive inhalational compounds is an important and still unresolved medical problem. Hazardous gases or vapors, e. g. chlorine, phosgene, sulfur mustard or methyl isocyanate, are released during occupational accidents or combustion processes and also represent a potential threat in terroristic scenarios. According to their broad-range chemical reactivity, the mechanism of lung injury evoked by these agents has long been described as rather unspecific. Consequently, therapeutic options are still restricted to symptomatic treatment. However, in recent years, ion channels of the transient receptor potential (TRP) family have been identified to act as specific sensor molecules expressed in the respiratory tract and to engage defined signaling pathways upon inhalational exposure to toxic challenges. These pulmonary receptor molecules have been primarily characterized in sensory neurons of the lung. However, chemosensory molecules are also expressed in non-neuronal cells, e.g. in the lung epithelium as well as in the pulmonary vasculature. Thus, activation of respiratory chemosensors by toxic inhalants promotes a complex signaling network directly or indirectly regulating pulmonary blood flow, the integrity of the epithelial lining, and the mucociliary clearance of the bronchial system. This review gives a synopsis on reactive lung-toxic agents and their specific target molecules in the lung and summarizes the current knowledge about the pathophysiological role of chemosensory signaling in neuronal and non-neuronal cells in toxic lung injury. Finally, we describe possible future strategies for a causal, specifically tailored treatment option based on the mechanistic understanding of molecular events ensuing inhalation of lung-toxic agents.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alexander SF (1947) Medical report on the Bari harbor mustard casualties. Mil Surg 101(1):1–17

    PubMed  CAS  Google Scholar 

  • Altenhofer S, Kleikers PW, Radermacher KA, Scheurer P, Rob Hermans JJ, Schiffers P, Ho H, Wingler K, Schmidt HH (2012) The NOX toolbox: validating the role of NADPH oxidases in physiology and disease. Cell Mol Life Sci: CMLS 69(14):2327–2343. doi:10.1007/s00018-012-1010-9

    PubMed  Google Scholar 

  • Amrani Y (2007) TNF-alpha and calcium signaling in airway smooth muscle cells: a never-ending story with promising therapeutic relevance. Am J Respir Cell Mol Biol 36(3):387–388. doi:36/3/387 [pii]

    PubMed  CAS  Google Scholar 

  • Andersson DA, Gentry C, Moss S, Bevan S (2008) Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci: The Official J Soc Neurosci 28(10):2485–2494. doi:10.1523/JNEUROSCI.5369-07.2008

    CAS  Google Scholar 

  • Andrade YN, Fernandes J, Vazquez E, Fernandez-Fernandez JM, Arniges M, Sanchez TM, Villalon M, Valverde MA (2005) TRPV4 channel is involved in the coupling of fluid viscosity changes to epithelial ciliary activity. J Cell Biol 168(6):869–874. doi:10.1083/jcb.200409070

    PubMed  CAS  Google Scholar 

  • Andre E, Campi B, Materazzi S, Trevisani M, Amadesi S, Massi D, Creminon C, Vaksman N, Nassini R, Civelli M, Baraldi PG, Poole DP, Bunnett NW, Geppetti P, Patacchini R (2008) Cigarette smoke-induced neurogenic inflammation is mediated by alpha, beta-unsaturated aldehydes and the TRPA1 receptor in rodents. J Clin Invest 118(7):2574–2582. doi:10.1172/JCI34886

    PubMed  CAS  Google Scholar 

  • Andre E, Gatti R, Trevisani M, Preti D, Baraldi PG, Patacchini R, Geppetti P (2009) Transient receptor potential ankyrin receptor 1 is a novel target for pro-tussive agents. Br J Pharmacol 158(6):1621–1628. doi:10.1111/j.1476-5381.2009.00438.x

    PubMed  CAS  Google Scholar 

  • Ban M, Langonne I, Huguet N, Pepin E, Morel G (2006) Inhaled chemicals may enhance allergic airway inflammation in ovalbumin-sensitised mice. Toxicology 226(2–3):161–171. doi:10.1016/j.tox.2006.06.012

    PubMed  CAS  Google Scholar 

  • Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41(6):849–857

    PubMed  CAS  Google Scholar 

  • Bang S, Kim KY, Yoo S, Kim YG, Hwang SW (2007) Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation. Eur J Neurosci 26(9):2516–2523. doi:10.1111/j.1460-9568.2007.05882.x

    PubMed  Google Scholar 

  • Banner KH, Igney F, Poll C (2011) TRP channels: emerging targets for respiratory disease. Pharmacol Ther 130(3):371–384. doi:10.1016/j.pharmthera.2011.03.005

    PubMed  CAS  Google Scholar 

  • Baraniuk JN, Kim D (2007) Nasonasal reflexes, the nasal cycle, and sneeze. Curr Allergy Asthma Rep 7(2):105–111

    PubMed  Google Scholar 

  • Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, Hogestatt ED, Julius D, Jordt SE, Zygmunt PM (2005) Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci USA 102(34):12248–12252. doi:10.1073/pnas.0505356102

    PubMed  CAS  Google Scholar 

  • Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124(6):1269–1282. doi:10.1016/j.cell.2006.02.023

    PubMed  CAS  Google Scholar 

  • Bessac BF, Jordt SE (2008) Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. Physiology 23:360–370. doi:10.1152/physiol.00026.2008

    PubMed  CAS  Google Scholar 

  • Bessac BF, Jordt SE (2010) Sensory detection and responses to toxic gases: mechanisms, health effects, and countermeasures. Proc Am Thorac Soc 7(4):269–277. doi:10.1513/pats.201001-004SM

    PubMed  CAS  Google Scholar 

  • Bessac BF, Sivula M, von Hehn CA, Escalera J, Cohn L, Jordt SE (2008) TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest 118(5):1899–1910. doi:10.1172/JCI34192

    PubMed  CAS  Google Scholar 

  • Bessac BF, Sivula M, von Hehn CA, Caceres AI, Escalera J, Jordt SE (2009) Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases. FASEB J: Official Publication Federation Am Soc Exper Biol 23(4):1102–1114. doi:10.1096/fj.08-117812

    CAS  Google Scholar 

  • Bielefeld EC, Hu BH, Harris KC, Henderson D (2005) Damage and threshold shift resulting from cochlear exposure to paraquat-generated superoxide. Hear Res 207(1–2):35–42. doi:10.1016/j.heares.2005.03.025

    PubMed  CAS  Google Scholar 

  • Bobb AJ, Arfsten DP, Jederberg WW (2005) N-acetyl-L-cysteine as prophylaxis against sulfur mustard. Mil Med 170(1):52–56

    PubMed  Google Scholar 

  • Bokemeyer C, Berger CC, Hartmann JT, Kollmannsberger C, Schmoll HJ, Kuczyk MA, Kanz L (1998) Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer. Br J Cancer 77(8):1355–1362

    PubMed  CAS  Google Scholar 

  • Bonner C (2008) Respiratory toxicity. In: Smart RC, Hodgson E (eds) Molecular and biochemical toxicology, 4th edn. Wiley, Hoboken, pp 639–670

    Google Scholar 

  • Brigelius-Flohe R, Flohe L (2011) Basic principles and emerging concepts in the redox control of transcription factors. Antioxid Redox Signal 15(8):2335–2381. doi:10.1089/ars.2010.3534

    PubMed  CAS  Google Scholar 

  • Brone B, Peeters PJ, Marrannes R, Mercken M, Nuydens R, Meert T, Gijsen HJ (2008) Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor. Toxicol Appl Pharmacol 231(2):150–156. doi:10.1016/j.taap. 2008.04.005

    PubMed  CAS  Google Scholar 

  • Brooks SM (2011) Perspective on the human cough reflex. Cough 7:10. doi:10.1186/1745-9974-7-10

    PubMed  Google Scholar 

  • Broughton E (2005) The bhopal disaster and its aftermath: a review. Environ Health: Global Access Sci Source 4(1):6. doi:10.1186/1476-069X-4-6

    Google Scholar 

  • Brozmanova M, Mazurova L, Ru F, Tatar M, Kollarik M (2012) Comparison of TRPA1-versus TRPV1-mediated cough in guinea pigs. Eur J Pharmacol 689(1–3):211–218. doi:10.1016/j.ejphar.2012.05.048

    PubMed  CAS  Google Scholar 

  • Bus JS, Gibson JE (1984) Paraquat: model for oxidant-initiated toxicity. Environ Health Perspect 55:37–46

    PubMed  CAS  Google Scholar 

  • Cahalan MD (2009) STIMulating store-operated Ca(2+) entry. Nat Cell Biol 11(6):669–677. doi:ncb0609-669 [pii]10.1038/ncb0609-669

    PubMed  CAS  Google Scholar 

  • Carnesecchi S, Deffert C, Donati Y, Basset O, Hinz B, Preynat-Seauve O, Guichard C, Arbiser JL, Banfi B, Pache JC, Barazzone-Argiroffo C, Krause KH (2011) A key role for NOX4 in epithelial cell death during development of lung fibrosis. Antioxid Redox Signal 15(3):607–619. doi:10.1089/ars.2010.3829

    PubMed  CAS  Google Scholar 

  • Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (1999) A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398(6726):436–441. doi:10.1038/18906

    PubMed  CAS  Google Scholar 

  • Cesare P, Moriondo A, Vellani V, McNaughton PA (1999) Ion channels gated by heat. Proc Natl Acad Sci USA 96(14):7658–7663

    PubMed  CAS  Google Scholar 

  • Cioffi DL, Lowe K, Alvarez DF, Barry C, Stevens T (2009) TRPing on the lung endothelium: calcium channels that regulate barrier function. Antioxid Redox Signal 11(4):765–776. doi:10.1089/ARS.2008.2221

    PubMed  CAS  Google Scholar 

  • Clapham DE, Runnels LW, Strubing C (2001) The TRP ion channel family. Nat Rev Neurosci 2(6):387–396. doi:10.1038/35077544

    PubMed  CAS  Google Scholar 

  • Cohen GM (1990) Pulmonary metabolism of foreign compounds: its role in metabolic activation. Environ Health Perspect 85:31–41

    PubMed  CAS  Google Scholar 

  • Colebatch HJ, Ng CK (1992) Estimating alveolar surface area during life. Respir Physiol 88(1–2): 163–170

    PubMed  CAS  Google Scholar 

  • Coleridge HM, Coleridge JC (1977) Impulse activity in afferent vagal C-fibres with endings in the intrapulmonary airways of dogs. Respir Physiol 29(2):125–142

    PubMed  CAS  Google Scholar 

  • Coleridge HM, Coleridge JC (1994) Pulmonary reflexes: neural mechanisms of pulmonary defense. Ann Rev Physiol 56:69–91. doi:10.1146/annurev.ph.56.030194.000441

    CAS  Google Scholar 

  • Coleridge HM, Coleridge JC, Luck JC (1965) Pulmonary afferent fibres of small diameter stimulated by capsaicin and by hyperinflation of the lungs. J Physiol 179(2):248–262

    PubMed  CAS  Google Scholar 

  • Comhair SA, Erzurum SC (2002) Antioxidant responses to oxidant-mediated lung diseases. Am J Physiol Lung Cell Mol Physiol 283(2):L246–L255. doi:10.1152/ajplung.00491.2001

    PubMed  CAS  Google Scholar 

  • Cristovao AC, Choi DH, Baltazar G, Beal MF, Kim YS (2009) The role of NADPH oxidase 1-derived reactive oxygen species in paraquat-mediated dopaminergic cell death. Antioxid Redox Signal 11(9):2105–2118. doi:10.1089/ARS.2009.2459

    PubMed  CAS  Google Scholar 

  • Cristovao AC, Guhathakurta S, Bok E, Je G, Yoo SD, Choi DH, Kim YS (2012) NADPH oxidase 1 mediates alpha-synucleinopathy in Parkinson’s disease. J Neurosci: Official J Soc Neurosci 32(42):14465–14477. doi:10.1523/JNEUROSCI.2246-12.2012

    CAS  Google Scholar 

  • Damann N, Rothermel M, Klupp BG, Mettenleiter TC, Hatt H, Wetzel CH (2006) Chemosensory properties of murine nasal and cutaneous trigeminal neurons identified by viral tracing. BMC Neurosci 7:46. doi:10.1186/1471-2202-7-46

    PubMed  Google Scholar 

  • Damann N, Owsianik G, Li S, Poll C, Nilius B (2009) The calcium-conducting ion channel transient receptor potential canonical 6 is involved in macrophage inflammatory protein-2-induced migration of mouse neutrophils. Acta Physiol (Oxf) 195(1):3–11. doi:APS1918 [pii]10.1111/j.1748-1716.2008.01918.x

    CAS  Google Scholar 

  • de Lange DW, Meulenbelt J (2011) Do corticosteroids have a role in preventing or reducing acute toxic lung injury caused by inhalation of chemical agents? Clin Toxicol 49(2):61–71. doi:10.3109/15563650.2011.553196

    Google Scholar 

  • Dhaka A, Uzzell V, Dubin AE, Mathur J, Petrus M, Bandell M, Patapoutian A (2009) TRPV1 is activated by both acidic and basic pH. J Neurosci: Official J Soc Neurosci 29(1):153–158. doi:10.1523/JNEUROSCI.4901-08.2009

    CAS  Google Scholar 

  • Dietrich A, Kalwa H, Rost BR, Gudermann T (2005) The diacylgylcerol-sensitive TRPC3/6/7 subfamily of cation channels: functional characterization and physiological relevance. Pflugers Archiv: Eur J Physiol 451(1):72–80. doi:10.1007/s00424-005-1460-0

    CAS  Google Scholar 

  • Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A (2006) A mutation in orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441(7090):179–185

    PubMed  CAS  Google Scholar 

  • Finney-Hayward TK, Popa MO, Bahra P, Li S, Poll CT, Gosling M, Nicholson AG, Russell RE, Kon OM, Jarai G, Westwick J, Barnes PJ, Donnelly LE (2010) Expression of transient receptor potential C6 channels in human lung macrophages. Am J Respir Cell Mol Biol 43(3):296–304. doi:10.1165/rcmb.2008-0373OC

    PubMed  CAS  Google Scholar 

  • Frasnelli J, Albrecht J, Bryant B, Lundstrom JN (2011) Perception of specific trigeminal chemosensory agonists. Neuroscience 189:377–383. doi:10.1016/j.neuroscience.2011.04.065

    PubMed  CAS  Google Scholar 

  • Fuchs B, Rupp M, Ghofrani HA, Schermuly RT, Seeger W, Grimminger F, Gudermann T, Dietrich A, Weissmann N (2011) Diacylglycerol regulates acute hypoxic pulmonary vasoconstriction via TRPC6. Respir Res 12:20. doi:10.1186/1465-9921-12-20

    PubMed  CAS  Google Scholar 

  • Fujita F, Uchida K, Moriyama T, Shima A, Shibasaki K, Inada H, Sokabe T, Tominaga M (2008) Intracellular alkalization causes pain sensation through activation of TRPA1 in mice. J Clin Invest 118(12):4049–4057. doi:10.1172/JCI35957

    PubMed  CAS  Google Scholar 

  • Fuller RW, Dixon CM, Barnes PJ (1985) Bronchoconstrictor response to inhaled capsaicin in humans. J Appl Physiol 58(4):1080–1084

    PubMed  CAS  Google Scholar 

  • Geppetti P, Patacchini R, Nassini R, Materazzi S (2010) Cough: the emerging role of the TRPA1 channel. Lung 188(Suppl 1):S63–68. doi:10.1007/s00408-009-9201-3

    PubMed  CAS  Google Scholar 

  • Gerhold KA, Bautista DM (2009) Molecular and cellular mechanisms of trigeminal chemosensation. Ann New York Acad Sci 1170:184–189. doi:10.1111/j.1749-6632.2009.03895.x

    CAS  Google Scholar 

  • Ghanei M, Shohrati M, Jafari M, Ghaderi S, Alaeddini F, Aslani J (2008) N-acetylcysteine improves the clinical conditions of mustard gas-exposed patients with normal pulmonary function test. Basic Clin Pharmacol Toxicol 103(5):428–432. doi:10.1111/j.1742-7843.2008.00318.x

    PubMed  CAS  Google Scholar 

  • Goel M, Sinkins WG, Schilling WP (2002) Selective association of TRPC channel subunits in rat brain synaptosomes. J Biol Chem 277(50):48303–48310

    PubMed  CAS  Google Scholar 

  • Grace M, Birrell MA, Dubuis E, Maher SA, Belvisi MG (2012) Transient receptor potential channels mediate the tussive response to prostaglandin E2 and bradykinin. Thorax 67(10): 891–900. doi:10.1136/thoraxjnl-2011-201443

    PubMed  Google Scholar 

  • Gradilone SA, Masyuk AI, Splinter PL, Banales JM, Huang BQ, Tietz PS, Masyuk TV, Larusso NF (2007) Cholangiocyte cilia express TRPV4 and detect changes in luminal tonicity inducing bicarbonate secretion. Proc Natl Acad Sci USA 104(48):19138–19143. doi:10.1073/pnas.0705964104

    PubMed  CAS  Google Scholar 

  • Grainge C, Rice P (2010) Management of phosgene-induced acute lung injury. Clin Toxicol 48(6): 497–508. doi:10.3109/15563650.2010.506877

    CAS  Google Scholar 

  • Guler AD, Lee H, Iida T, Shimizu I, Tominaga M, Caterina M (2002) Heat-evoked activation of the ion channel, TRPV4. J Neurosci: Official J Soc Neurosci 22(15):6408–6414. doi:20026679

    CAS  Google Scholar 

  • Hanaoka S, Nomura K, Wada T (2006) Determination of mustard and lewisite related compounds in abandoned chemical weapons (yellow shells) from sources in China and Japan. J Chromatogr A 1101(1–2):268–277. doi:10.1016/j.chroma.2005.10.028

    PubMed  CAS  Google Scholar 

  • Hardie RC, Minke B (1992) The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors. Neuron 8(4):643–651

    PubMed  CAS  Google Scholar 

  • Hecker L, Cheng J, Thannickal VJ (2012) Targeting NOX enzymes in pulmonary fibrosis. Cell Mol Life Sci: CMLS 69(14):2365–2371. doi:10.1007/s00018-012-1012-7

    PubMed  CAS  Google Scholar 

  • HELCOM (1994) Report on chemical munitions dumped in the Baltic Sea, Report to the 15th meeting of Helsinki Commission. Danish Environmental Protection Agency

    Google Scholar 

  • Hill K, Schaefer M (2009) Ultraviolet light and photosensitising agents activate TRPA1 via generation of oxidative stress. Cell Calcium 45(2):155–164. doi:10.1016/j.ceca.2008.08.001

    PubMed  CAS  Google Scholar 

  • Hinman A, Chuang HH, Bautista DM, Julius D (2006) TRP channel activation by reversible covalent modification. Proc Natl Acad Sci USA 103(51):19564–19568. doi:10.1073/pnas.0609598103

    PubMed  CAS  Google Scholar 

  • Hirata H, Oshinsky ML (2012) Ocular dryness excites two classes of corneal afferent neurons implicated in basal tearing in rats: involvement of transient receptor potential channels. J Neurophysiol 107(4):1199–1209. doi:10.1152/jn.00657.2011

    PubMed  CAS  Google Scholar 

  • Hisatsune C, Kuroda Y, Nakamura K, Inoue T, Nakamura T, Michikawa T, Mizutani A, Mikoshiba K (2004) Regulation of TRPC6 channel activity by tyrosine phosphorylation. J Biol Chem 279(18):18887–18894

    PubMed  CAS  Google Scholar 

  • Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G (1999) Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature 397(6716):259–263. doi:10.1038/16711

    PubMed  CAS  Google Scholar 

  • Hofmann T, Schaefer M, Schultz G, Gudermann T (2000) Transient receptor potential channels as molecular substrates of receptor-mediated cation entry. J Mol Med (Berl) 78(1):14–25

    CAS  Google Scholar 

  • Hofmann T, Schaefer M, Schultz G, Gudermann T (2002) Subunit composition of mammalian transient receptor potential channels in living cells. Proc Natl Acad Sci USA 99(11): 7461–7466. doi:10.1073/pnas.102596199

    PubMed  CAS  Google Scholar 

  • Jian MY, King JA, Al-Mehdi AB, Liedtke W, Townsley MI (2008) High vascular pressure-induced lung injury requires P450 epoxygenase-dependent activation of TRPV4. Am J Respir Cell Mol Biol 38(4):386–392. doi:10.1165/rcmb.2007-0192OC

    PubMed  CAS  Google Scholar 

  • Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID, Julius D (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427(6971):260–265. doi:10.1038/nature02282

    PubMed  CAS  Google Scholar 

  • Jugg BJ, Smith AJ, Rudall SJ, Rice P (2011) The injured lung: clinical issues and experimental models. Phil Trans Royal Soc Lond Series B Biol Sci 366(1562):306–309. doi:10.1098/rstb.2010.0235

    CAS  Google Scholar 

  • Karashima Y, Damann N, Prenen J, Talavera K, Segal A, Voets T, Nilius B (2007) Bimodal action of menthol on the transient receptor potential channel TRPA1. The J Neurosci: Official J Soc Neurosci 27(37):9874–9884. doi:10.1523/JNEUROSCI.2221-07.2007

    CAS  Google Scholar 

  • Kawasaki BT, Liao Y, Birnbaumer L (2006) Role of Src in C3 transient receptor potential channel function and evidence for a heterogeneous makeup of receptor- and store-operated Ca2+ entry channels. Proc Natl Acad Sci USA 103(2):335–340

    PubMed  CAS  Google Scholar 

  • Kehe K, Szinicz L (2005) Medical aspects of sulphur mustard poisoning. Toxicology 214(3): 198–209. doi:10.1016/j.tox.2005.06.014

    PubMed  CAS  Google Scholar 

  • Kinoshita H, Kuwahara K, Nishida M, Jian Z, Rong X, Kiyonaka S, Kuwabara Y, Kurose H, Inoue R, Mori Y, Li Y, Nakagawa Y, Usami S, Fujiwara M, Yamada Y, Minami T, Ueshima K, Nakao K (2010) Inhibition of TRPC6 channel activity contributes to the antihypertrophic effects of natriuretic peptides-guanylyl cyclase-A signaling in the heart. Circ Res 106(12): 1849–1860. doi:10.1161/CIRCRESAHA.109.208314

    PubMed  CAS  Google Scholar 

  • Koitabashi N, Aiba T, Hesketh GG, Rowell J, Zhang M, Takimoto E, Tomaselli GF, Kass DA (2010) Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation Novel mechanism of cardiac stress modulation by PDE5 inhibition. J Mol Cell Cardiol 48(4):713–724. doi:10.1016/j.yjmcc.2009.11.015

    PubMed  CAS  Google Scholar 

  • Kunichika N, Yu Y, Remillard CV, Platoshyn O, Zhang S, Yuan JX (2004) Overexpression of TRPC1 enhances pulmonary vasoconstriction induced by capacitative Ca2+ entry. Am J Physiol Lung Cell Mol Physiol 287(5):L962–L969

    PubMed  CAS  Google Scholar 

  • Kwan HY, Huang Y, Yao X (2004) Regulation of canonical transient receptor potential isoform 3 (TRPC3) channel by protein kinase G. Proc Nat Acad Sci USA 101(8):2625–2630. doi:101/8/2625 [pii]

    PubMed  CAS  Google Scholar 

  • Lassegue B, San Martin A, Griendling KK (2012) Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res 110(10):1364–1390. doi:10.1161/CIRCRESAHA.111.243972

    PubMed  CAS  Google Scholar 

  • Lee IT, Yang CM (2012) Role of NADPH oxidase/ROS in pro-inflammatory mediators-induced airway and pulmonary diseases. Biochem Pharmacol 84(5):581–590. doi:10.1016/j.bcp. 2012.05.005

    PubMed  CAS  Google Scholar 

  • Lembrechts R, Brouns I, Schnorbusch K, Pintelon I, Timmermans JP, Adriaensen D (2012) Neuroepithelial bodies as mechanotransducers in the intrapulmonary airway epithelium: involvement of TRPC5. Am J Respir Cell Mol Biol 47(3):315–323. doi:10.1165/rcmb.2012-0068OC

    PubMed  CAS  Google Scholar 

  • Li S, Westwick J, Poll C (2003) Transient receptor potential (TRP) channels as potential drug targets in respiratory disease. Cell Calcium 33(5–6):551–558. doi:S0143416003000605 [pii]

    PubMed  CAS  Google Scholar 

  • Liao Y, Plummer NW, George MD, Abramowitz J, Zhu MX, Birnbaumer L (2009) A role for Orai in TRPC-mediated Ca2+ entry suggests that a TRPC:Orai complex may mediate store and receptor operated Ca2+ entry. Proc Nat Acad Sci USA 106(9):3202–3206. doi:0813346106 [pii]10.1073/pnas.0813346106

    PubMed  CAS  Google Scholar 

  • Liedtke W (2007) TRPV channels’ role in osmotransduction and mechanotransduction. Handb Exper Pharmacol 179:473–487. doi:10.1007/978-3-540-34891-7_28

    CAS  Google Scholar 

  • Lin MJ, Leung GP, Zhang WM, Yang XR, Yip KP, Tse CM, Sham JS (2004) Chronic hypoxia-induced upregulation of store-operated and receptor-operated Ca2+ channels in pulmonary arterial smooth muscle cells: a novel mechanism of hypoxic pulmonary hypertension. Circ Res 95(5):496–505. doi:10.1161/01.RES.0000138952.16382.ad

    PubMed  CAS  Google Scholar 

  • Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE Jr, Meyer T (2005) STIM is a Ca2+ sensor essential for Ca2+−store-depletion-triggered Ca2+ influx. Curr Biol 15(13):1235–1241

    PubMed  CAS  Google Scholar 

  • Lorenzo IM, Liedtke W, Sanderson MJ, Valverde MA (2008) TRPV4 channel participates in receptor-operated calcium entry and ciliary beat frequency regulation in mouse airway epithelial cells. Proc Natl Acad Sci USA 105(34):12611–12616. doi:10.1073/pnas.0803970105

    PubMed  CAS  Google Scholar 

  • Lundberg JM, Brodin E, Hua X, Saria A (1984) Vascular permeability changes and smooth muscle contraction in relation to capsaicin-sensitive substance P afferents in the guinea-pig. Acta Physiol Scand 120(2):217–227

    PubMed  CAS  Google Scholar 

  • Lundblad L, Saria A, Lundberg JM, Anggard A (1983) Increased vascular permeability in rat nasal mucosa induced by substance P and stimulation of capsaicin-sensitive trigeminal neurons. Acta Otolaryngol 96(5–6):479–484

    PubMed  CAS  Google Scholar 

  • Macpherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG, Cravatt BF, Patapoutian A (2007a) Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature 445(7127):541–545. doi:10.1038/nature05544

    PubMed  CAS  Google Scholar 

  • Macpherson LJ, Xiao B, Kwan KY, Petrus MJ, Dubin AE, Hwang S, Cravatt B, Corey DP, Patapoutian A (2007b) An ion channel essential for sensing chemical damage. J Neurosci: Official J Soc Neurosci 27(42):11412–11415. doi:10.1523/JNEUROSCI.3600-07.2007

    CAS  Google Scholar 

  • Malis DD, Rist B, Nicoucar K, Beck-Sickinger AG, Morel DR, Lacroix JS (2001) Modulatory effect of two novel CGRP receptor antagonists on nasal vasodilatatory responses to exogenous CGRP, capsaicin, bradykinin and histamine in anaesthetised pigs. Regul Pept 101(1–3):101–108

    PubMed  CAS  Google Scholar 

  • Materazzi S, Nassini R, Gatti R, Trevisani M, Geppetti P (2009) Cough sensors. II. Transient receptor potential membrane receptors on cough sensors. Handb Exper Pharmacol 187:49–61. doi:10.1007/978-3-540-79842-2_3

    CAS  Google Scholar 

  • Matta JA, Cornett PM, Miyares RL, Abe K, Sahibzada N, Ahern GP (2008) General anesthetics activate a nociceptive ion channel to enhance pain and inflammation. Proc Natl Acad Sci USA 105(25):8784–8789. doi:10.1073/pnas.0711038105

    PubMed  CAS  Google Scholar 

  • McKemy DD, Neuhausser WM, Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416(6876):52–58. doi:10.1038/nature719

    PubMed  CAS  Google Scholar 

  • McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM (2007) TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci USA 104(33):13525–13530. doi:10.1073/pnas.0705924104

    PubMed  CAS  Google Scholar 

  • Mergler S, Garreis F, Sahlmuller M, Reinach PS, Paulsen F, Pleyer U (2011) Thermosensitive transient receptor potential channels in human corneal epithelial cells. J Cell Physiol 226(7): 1828–1842. doi:10.1002/jcp. 22514

    PubMed  CAS  Google Scholar 

  • Miller K, Chang A (2003) Acute inhalation injury. Emerg Med Clin North Am 21(2):533–557

    PubMed  Google Scholar 

  • Minke B (1977) Drosophila mutant with a transducer defect. Biophys Struct Mech 3(1):59–64

    PubMed  CAS  Google Scholar 

  • Montell C, Rubin GM (1989) Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2(4):1313–1323

    PubMed  CAS  Google Scholar 

  • Montell C, Jones K, Hafen E, Rubin G (1985) Rescue of the Drosophila phototransduction mutation trp by germline transformation. Science 230(4729):1040–1043

    PubMed  CAS  Google Scholar 

  • Montell C, Birnbaumer L, Flockerzi V (2002) The TRP channels, a remarkably functional family. Cell 108(5):595–598

    PubMed  CAS  Google Scholar 

  • Muhle H, McClellan R (2003) Respirationstrakt. In: Marquardt H, Schäfer S (eds) Lehrbuch der Toxikologie, vol 2. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, pp 365–382

    Google Scholar 

  • Mukhopadhyay I, Gomes P, Aranake S, Shetty M, Karnik P, Damle M, Kuruganti S, Thorat S, Khairatkar-Joshi N (2011) Expression of functional TRPA1 receptor on human lung fibroblast and epithelial cells. J Recept Signal Transduct Res 31(5):350–358. doi:10.3109/10799893.2011.602413

    PubMed  CAS  Google Scholar 

  • Muller T, Hengstermann A (2012) Nrf2: friend and foe in preventing cigarette smoking-dependent lung disease. Chem Res Toxicol 25(9):1805–1824. doi:10.1021/tx300145n

    PubMed  Google Scholar 

  • Murata Y, Masuko S (2006) Peripheral and central distribution of TRPV1, substance P and CGRP of rat corneal neurons. Brain Res 1085(1):87–94. doi:10.1016/j.brainres.2006.02.035

    PubMed  CAS  Google Scholar 

  • Nilius B, Owsianik G (2011) The transient receptor potential family of ion channels. Genome Biol 12(3):218. doi:10.1186/gb-2011-12-3-218

    PubMed  CAS  Google Scholar 

  • Nishida M, Watanabe K, Sato Y, Nakaya M, Kitajima N, Ide T, Inoue R, Kurose H (2010) Phosphorylation of TRPC6 channels at Thr69 is required for anti-hypertrophic effects of phosphodiesterase 5 inhibition. J Biol Chem 285(17):13244–13253. doi:10.1074/jbc.M109.074104

    PubMed  CAS  Google Scholar 

  • Okada T, Inoue R, Yamazaki K, Maeda A, Kurosaki T, Yamakuni T, Tanaka I, Shimizu S, Ikenaka K, Imoto K, Mori Y (1999) Molecular and functional characterization of a novel mouse transient receptor potential protein homologue TRP7. Ca(2+)-permeable cation channel that is constitutively activated and enhanced by stimulation of G protein-coupled receptor. J Biol Chem 274(39):27359–27370

    PubMed  CAS  Google Scholar 

  • Owsianik G, Talavera K, Voets T, Nilius B (2006) Permeation and selectivity of TRP channels. Ann Rev Physiol 68:685–717. doi:10.1146/annurev.physiol.68.040204.101406

    CAS  Google Scholar 

  • Paffenholz R, Bergstrom RA, Pasutto F, Wabnitz P, Munroe RJ, Jagla W, Heinzmann U, Marquardt A, Bareiss A, Laufs J, Russ A, Stumm G, Schimenti JC, Bergstrom DE (2004) Vestibular defects in head-tilt mice result from mutations in Nox3, encoding an NADPH oxidase. Genes Dev 18(5):486–491. doi:10.1101/gad.1172504

    PubMed  CAS  Google Scholar 

  • Parra A, Madrid R, Echevarria D, del Olmo S, Morenilla-Palao C, Acosta MC, Gallar J, Dhaka A, Viana F, Belmonte C (2010) Ocular surface wetness is regulated by TRPM8-dependent cold thermoreceptors of the cornea. Nat Med 16(12):1396–1399. doi:10.1038/nm.2264

    PubMed  CAS  Google Scholar 

  • Pedersen SF, Owsianik G, Nilius B (2005) TRP channels: an overview. Cell Calcium 38(3–4): 233–252. doi:10.1016/j.ceca.2005.06.028

    PubMed  CAS  Google Scholar 

  • Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A (2002a) A TRP channel that senses cold stimuli and menthol. Cell 108(5):705–715

    PubMed  CAS  Google Scholar 

  • Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ, Hergarden AC, Story GM, Colley S, Hogenesch JB, McIntyre P, Bevan S, Patapoutian A (2002b) A heat-sensitive TRP channel expressed in keratinocytes. Science 296(5575):2046–2049. doi:10.1126/science.1073140

    PubMed  CAS  Google Scholar 

  • Perez CA, Huang L, Rong M, Kozak JA, Preuss AK, Zhang H, Max M, Margolskee RF (2002) A transient receptor potential channel expressed in taste receptor cells. Nat Neurosci 5(11): 1169–1176. doi:10.1038/nn952

    PubMed  CAS  Google Scholar 

  • Petersson G, Malm L, Ekman R, Hakanson R (1989) Capsaicin evokes secretion of nasal fluid and depletes substance P and calcitonin gene-related peptide from the nasal mucosa in the rat. Br J Pharmacol 98(3):930–936

    PubMed  CAS  Google Scholar 

  • Plant TD, Strotmann R (2007) Trpv4. Handb Exper Pharmacol 179:189–205. doi:10.1007/978-3-540-34891-7_11

    CAS  Google Scholar 

  • Pohl C, Papritz M, Moisch M, Wubbeke C, Hermanns MI, Uboldi C, Dei-Anang J, Mayer E, Kirkpatrick CJ, Kehe K (2009) Acute morphological and toxicological effects in a human bronchial coculture model after sulfur mustard exposure. Toxicol Sci: Official J Soc Toxicol 112(2):482–489. doi:10.1093/toxsci/kfp211

    CAS  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(6):663–695. doi:10.1517/13543776.2012.696099

    PubMed  CAS  Google Scholar 

  • Quirce S, Barranco P (2010) Cleaning agents and asthma. J Invest Allergol Clin Immunol: Official Organ Inter Assoc Asthmol 20(7):542–550; quiz 542p following 550

    CAS  Google Scholar 

  • Reichenberger F, Voswinckel R, Enke B, Rutsch M, El Fechtali E, Schmehl T, Olschewski H, Schermuly R, Weissmann N, Ghofrani HA, Grimminger F, Mayer E, Seeger W (2007) Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension. Eur Respir J: Official J Eur Soc Clin Respir Physiol 30(5):922–927. doi:10.1183/09031936.00039007

    CAS  Google Scholar 

  • Riteau N, Gasse P, Fauconnier L, Gombault A, Couegnat M, Fick L, Kanellopoulos J, Quesniaux VF, Marchand-Adam S, Crestani B, Ryffel B, Couillin I (2010) Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am J Respir Crit Care Med 182(6):774–783. doi:10.1164/rccm.201003-0359OC

    PubMed  CAS  Google Scholar 

  • Robbins A, Kurose M, Winterson BJ, Meng ID (2012) Menthol activation of corneal cool cells induces TRPM8-mediated lacrimation but not nociceptive responses in rodents. Invest Ophthalmol Vis Sci 53(11):7034–7042. doi:10.1167/iovs.12-10025

    PubMed  CAS  Google Scholar 

  • Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Velicelebi G, Stauderman KA (2005) STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol 169(3):435–445

    PubMed  CAS  Google Scholar 

  • Rybak LP, Mukherjea D, Jajoo S, Kaur T, Ramkumar V (2012) siRNA-mediated knock-down of NOX3: therapy for hearing loss? Cell Mol Life Sci: CMLS 69(14):2429–2434. doi:10.1007/s00018-012-1016-3

    PubMed  CAS  Google Scholar 

  • Salathe M, Bookman RJ (1995) Coupling of [Ca2+]i and ciliary beating in cultured tracheal epithelial cells. J Cell Sci 108(Pt 2):431–440

    PubMed  CAS  Google Scholar 

  • Salazar H, Llorente I, Jara-Oseguera A, Garcia-Villegas R, Munari M, Gordon SE, Islas LD, Rosenbaum T (2008) A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic. Nat Neurosci 11(3):255–261. doi:10.1038/nn2056

    PubMed  CAS  Google Scholar 

  • Samal A, Honovar J, White CR, Patel RP (2010) Potential for chlorine gas-induced injury in the extrapulmonary vasculature. Proc Am Thorac Soc 7(4):290–293. doi:10.1513/pats.201001-006SM

    PubMed  CAS  Google Scholar 

  • Sanderson H, Fauser P, Thomsen M, Sorensen PB (2008) Screening level fish community risk assessment of chemical warfare agents in the Baltic Sea. J Hazard Mater 154(1–3):846–857. doi:10.1016/j.jhazmat.2007.10.117

    PubMed  CAS  Google Scholar 

  • Sanderson H, Fauser P, Thomsen M, Vanninen P, Soderstrom M, Savin Y, Khalikov I, Hirvonen A, Niiranen S, Missiaen T, Gress A, Borodin P, Medvedeva N, Polyak Y, Paka V, Zhurbas V, Feller P (2010) Environmental hazards of sea-dumped chemical weapons. Environ Sci Technol 44(12):4389–4394. doi:10.1021/es903472a

    PubMed  CAS  Google Scholar 

  • Sawada Y, Hosokawa H, Matsumura K, Kobayashi S (2008) Activation of transient receptor potential ankyrin 1 by hydrogen peroxide. Eur J Neurosci 27(5):1131–1142. doi:10.1111/j.1460-9568.2008.06093.x

    PubMed  Google Scholar 

  • Seki N, Shirasaki H, Kikuchi M, Sakamoto T, Watanabe N, Himi T (2006) Expression and localization of TRPV1 in human nasal mucosa. Rhinology 44(2):128–134

    PubMed  Google Scholar 

  • Seki N, Shirasaki H, Kikuchi M, Himi T (2007) Capsaicin induces the production of IL-6 in human upper respiratory epithelial cells. Life Sci 80(17):1592–1597. doi:10.1016/j.lfs.2007.01.037

    PubMed  CAS  Google Scholar 

  • Sel S, Rost BR, Yildirim AO, Sel B, Kalwa H, Fehrenbach H, Renz H, Gudermann T, Dietrich A (2008) Loss of classical transient receptor potential 6 channel reduces allergic airway response. Clin Exp Allergy 38(9):1548–1558

    PubMed  CAS  Google Scholar 

  • Seminario-Vidal L, Okada SF, Sesma JI, Kreda SM, van Heusden CA, Zhu Y, Jones LC, O'Neal WK, Penuela S, Laird DW, Boucher RC, Lazarowski ER (2011) Rho signaling regulates pannexin 1-mediated ATP release from airway epithelia. J Biol Chem 286(30):26277–26286. doi:10.1074/jbc.M111.260562

    PubMed  CAS  Google Scholar 

  • Shusterman D (1999) Upper and lower airway sequelae of irritant inhalations. Clin Pulm Med 6(1):18–31

    Google Scholar 

  • Smit LA, Kogevinas M, Anto JM, Bouzigon E, Gonzalez JR, Le Moual N, Kromhout H, Carsin AE, Pin I, Jarvis D, Vermeulen R, Janson C, Heinrich J, Gut I, Lathrop M, Valverde MA, Demenais F, Kauffmann F (2012) Transient receptor potential genes, smoking, occupational exposures and cough in adults. Respir Res 13:26. doi:10.1186/1465-9921-13-26

    PubMed  Google Scholar 

  • Smith BR, Brian WR (1991) The role of metabolism in chemical-induced pulmonary toxicity. Toxicol Pathol 19(4 Pt 1):470–481

    PubMed  CAS  Google Scholar 

  • Smith GD, Gunthorpe MJ, Kelsell RE, Hayes PD, Reilly P, Facer P, Wright JE, Jerman JC, Walhin JP, Ooi L, Egerton J, Charles KJ, Smart D, Randall AD, Anand P, Davis JB (2002) TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 418(6894):186–190. doi:10.1038/nature00894

    PubMed  CAS  Google Scholar 

  • Stone KC, Mercer RR, Gehr P, Stockstill B, Crapo JD (1992) Allometric relationships of cell numbers and size in the mammalian lung. Am J Respir Cell Mol Biol 6(2):235–243

    PubMed  CAS  Google Scholar 

  • Storch U, Forst AL, Philipp M, Gudermann T, Mederos y Schnitzler M (2012) Transient receptor potential channel 1 (TRPC1) reduces calcium permeability in heteromeric channel complexes. J Biol Chem 287(5):3530–3540. doi:10.1074/jbc.M111.283218

    PubMed  CAS  Google Scholar 

  • Strubing C, Krapivinsky G, Krapivinsky L, Clapham DE (2001) TRPC1 and TRPC5 form a novel cation channel in mammalian brain. Neuron 29(3):645–655

    PubMed  CAS  Google Scholar 

  • Strubing C, Krapivinsky G, Krapivinsky L, Clapham DE (2003) Formation of novel TRPC channels by complex subunit interactions in embryonic brain. J Biol Chem 278(40): 39014–39019

    PubMed  Google Scholar 

  • Sweeney M, McDaniel SS, Platoshyn O, Zhang S, Yu Y, Lapp BR, Zhao Y, Thistlethwaite PA, Yuan JX (2002a) Role of capacitative Ca2+ entry in bronchial contraction and remodeling. J Appl Physiol 92(4):1594–1602

    PubMed  CAS  Google Scholar 

  • Sweeney M, Yu Y, Platoshyn O, Zhang S, McDaniel SS, Yuan JX (2002b) Inhibition of endogenous TRP1 decreases capacitative Ca2+ entry and attenuates pulmonary artery smooth muscle cell proliferation. Am J Physiol Lung Cell Mol Physiol 283(1):L144–L155

    PubMed  CAS  Google Scholar 

  • Symanowicz PT, Gianutsos G, Morris JB (2004) Lack of role for the vanilloid receptor in response to several inspired irritant air pollutants in the C57Bl/6J mouse. Neurosci Lett 362(2):150–153. doi:10.1016/j.neulet.2004.03.016

    PubMed  CAS  Google Scholar 

  • Takahashi N, Mizuno Y, Kozai D, Yamamoto S, Kiyonaka S, Shibata T, Uchida K, Mori Y (2008a) Molecular characterization of TRPA1 channel activation by cysteine-reactive inflammatory mediators. Channels 2(4):287–298

    PubMed  Google Scholar 

  • Takahashi S, Lin H, Geshi N, Mori Y, Kawarabayashi Y, Takami N, Mori MX, Honda A, Inoue R (2008b) Nitric oxide-cGMP-protein kinase G pathway negatively regulates vascular transient receptor potential channel TRPC6. J Physiol 586(Pt 17):4209–4223. doi:156083 [pii]10.1113/jphysiol.2008.156083

    PubMed  CAS  Google Scholar 

  • Takahashi N, Kuwaki T, Kiyonaka S, Numata T, Kozai D, Mizuno Y, Yamamoto S, Naito S, Knevels E, Carmeliet P, Oga T, Kaneko S, Suga S, Nokami T, Yoshida J, Mori Y (2011) TRPA1 underlies a sensing mechanism for O2. Nat Chem Biol 7(10):701–711. doi:10.1038/nchembio.640

    PubMed  CAS  Google Scholar 

  • Takahashi N, Kozai D, Mori Y (2012) TRP channels: sensors and transducers of gasotransmitter signals. Frontiers Physiol 3:324. doi:10.3389/fphys.2012.00324

    CAS  Google Scholar 

  • Talavera K, Yasumatsu K, Voets T, Droogmans G, Shigemura N, Ninomiya Y, Margolskee RF, Nilius B (2005) Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature 438(7070):1022–1025. doi:10.1038/nature04248

    PubMed  CAS  Google Scholar 

  • Talavera K, Gees M, Karashima Y, Meseguer VM, Vanoirbeek JA, Damann N, Everaerts W, Benoit M, Janssens A, Vennekens R, Viana F, Nemery B, Nilius B, Voets T (2009) Nicotine activates the chemosensory cation channel TRPA1. Nat Neurosci 12(10):1293–1299. doi:10.1038/nn.2379

    PubMed  CAS  Google Scholar 

  • Taylor-Clark TE, Ghatta S, Bettner W, Undem BJ (2009) Nitrooleic acid, an endogenous product of nitrative stress, activates nociceptive sensory nerves via the direct activation of TRPA1. Mol Pharmacol 75(4):820–829. doi:10.1124/mol.108.054445

    PubMed  CAS  Google Scholar 

  • Thurlbeck WM (1967) The internal surface area of nonemphysematous lungs. Am Rev Respir Dis 95(5):765–773

    PubMed  CAS  Google Scholar 

  • Tiruppathi C, Freichel M, Vogel SM, Paria BC, Mehta D, Flockerzi V, Malik AB (2002) Impairment of store-operated Ca2+ entry in TRPC4(−/−) mice interferes with increase in lung microvascular permeability. Circ Res 91(1):70–76

    PubMed  CAS  Google Scholar 

  • Tominaga M (2007) The role of TRP channels in thermosensation. In: Liedtke WB, Heller S (eds) TRP ion channel function in sensory transduction and cellular signaling cascades. CRC Press, Boca Raton

    Google Scholar 

  • Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21(3):531–543

    PubMed  CAS  Google Scholar 

  • Trebak M, Hempel N, Wedel BJ, Smyth JT, Bird GS, Putney JW Jr (2005) Negative regulation of TRPC3 channels by protein kinase C-mediated phosphorylation of serine 712. Mol Pharmacol 67(2):558–563

    PubMed  CAS  Google Scholar 

  • Trevisani M, Siemens J, Materazzi S, Bautista DM, Nassini R, Campi B, Imamachi N, Andre E, Patacchini R, Cottrell GS, Gatti R, Basbaum AI, Bunnett NW, Julius D, Geppetti P (2007) 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci USA 104(33): 13519–13524. doi:10.1073/pnas.0705923104

    PubMed  CAS  Google Scholar 

  • Tuorinsky S, Sciuto A (2008) Toxic inhalation injury and toxic industrial chemicals. In: Lenhart M (ed) Medical aspects of chemical warfare. Office of the General Surgeon, Washington, DC, pp 339–370

    Google Scholar 

  • Urbanetti J (1997) Toxic inhalation injury. In: Sidell F, Takafuji E, Franz D (eds) Medical aspects of chemical and biological warfare. Office of the Surgeon General, Washington, DC, pp 247–270

    Google Scholar 

  • Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP (2006) CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science 312(5777):1220–1223. doi:1127883 [pii]10.1126/science.1127883

    PubMed  CAS  Google Scholar 

  • Wang S, Dai Y, Fukuoka T, Yamanaka H, Kobayashi K, Obata K, Cui X, Tominaga M, Noguchi K (2008) Phospholipase C and protein kinase A mediate bradykinin sensitization of TRPA1: a molecular mechanism of inflammatory pain. Brain: J Neurol 131(Pt 5):1241–1251. doi:10.1093/brain/awn060

    Google Scholar 

  • Watanabe H, Vriens J, Suh SH, Benham CD, Droogmans G, Nilius B (2002) Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells. J Biol Chem 277(49):47044–47051. doi:10.1074/jbc.M208277200

    PubMed  CAS  Google Scholar 

  • Weinberger B, Laskin JD, Sunil VR, Sinko PJ, Heck DE, Laskin DL (2011) Sulfur mustard-induced pulmonary injury: therapeutic approaches to mitigating toxicity. Pulm Pharmacol Ther 24(1): 92–99. doi:10.1016/j.pupt.2010.09.004

    PubMed  CAS  Google Scholar 

  • Weissmann N, Dietrich A, Fuchs B, Kalwa H, Ay M, Dumitrascu R, Olschewski A, Storch U, Mederos y Schnitzler M, Ghofrani HA, Schermuly RT, Pinkenburg O, Seeger W, Grimminger F, Gudermann T (2006) Classical transient receptor potential channel 6 (TRPC6) is essential for hypoxic pulmonary vasoconstriction and alveolar gas exchange. Proc Nat Acad Sci USA 103(50):19093–19098

    PubMed  CAS  Google Scholar 

  • Weissmann N, Sydykov A, Kalwa H, Storch U, Fuchs B, Mederos y Schnitzler M, Brandes RP, Grimminger F, Meissner M, Freichel M, Offermanns S, Veit F, Pak O, Krause KH, Schermuly RT, Brewer AC, Schmidt HH, Seeger W, Shah AM, Gudermann T, Ghofrani HA, Dietrich A (2012) Activation of TRPC6 channels is essential for lung ischaemia-reperfusion induced oedema in mice. Nature Commun 3:649. doi:10.1038/ncomms1660

    Google Scholar 

  • White TA, Xue A, Chini EN, Thompson M, Sieck GC, Wylam ME (2006) Role of transient receptor potential C3 in TNF-alpha-enhanced calcium influx in human airway myocytes. Am J Respir Cell Mol Biol 35(2):243–251. doi:2006-0003OC [pii]10.1165/rcmb.2006-0003OC

    PubMed  CAS  Google Scholar 

  • Xu H, Ramsey IS, Kotecha SA, Moran MM, Chong JA, Lawson D, Ge P, Lilly J, Silos-Santiago I, Xie Y, DiStefano PS, Curtis R, Clapham DE (2002) TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418(6894):181–186. doi:10.1038/nature00882

    PubMed  CAS  Google Scholar 

  • Yin J, Kuebler WM (2010) Mechanotransduction by TRP channels: general concepts and specific role in the vasculature. Cell Biochem Biophys 56(1):1–18. doi:10.1007/s12013-009-9067-2

    PubMed  CAS  Google Scholar 

  • Yu Y, Fantozzi I, Remillard CV, Landsberg JW, Kunichika N, Platoshyn O, Tigno DD, Thistlethwaite PA, Rubin LJ, Yuan JX (2004) Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc Natl Acad Sci USA 101(38):13861–13866

    PubMed  CAS  Google Scholar 

  • Yu Y, Keller SH, Remillard CV, Safrina O, Nicholson A, Zhang SL, Jiang W, Vangala N, Landsberg JW, Wang JY, Thistlethwaite PA, Channick RN, Robbins IM, Loyd JE, Ghofrani HA, Grimminger F, Schermuly RT, Cahalan MD, Rubin LJ, Yuan JX (2009) A functional single-nucleotide polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension. Circulation 119(17):2313–2322. doi:10.1161/CIRCULATIONAHA.108.782458

    PubMed  CAS  Google Scholar 

  • Yuan JP, Kim MS, Zeng W, Shin DM, Huang G, Worley PF, Muallem S (2009a) TRPC channels as STIM1-regulated SOCs. Channels 3(4):9198 [pii]

    Google Scholar 

  • Yuan JP, Zeng W, Dorwart MR, Choi YJ, Worley PF, Muallem S (2009b) SOAR and the polybasic STIM1 domains gate and regulate Orai channels. Nat Cell Biol 11(3):337–343. doi:ncb1842 [pii]10.1038/ncb1842

    PubMed  CAS  Google Scholar 

  • Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ (2003) Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112(3):293–301

    PubMed  CAS  Google Scholar 

  • Zhang SL, Yu Y, Roos J, Kozak JA, Deerinck TJ, Ellisman MH, Stauderman KA, Cahalan MD (2005) STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature 437(7060):902–905

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rudolf Boehm-Institut für Pharmakologie und Toxikologie, Selbständige Abteilung für Klinische Pharmakologie, Universität Leipzig, Härtelstr. 16-18, Leipzig, 04107, Germany

    Thomas Büch

  2. Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, Goethestr. 33, München, 80336, Germany

    Thomas Büch & Dirk Steinritz

  3. Walther-Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, Comprehensive Pneumology Center Munich (CPC-M), Goethestrasse 33, München, 80336, Germany

    Eva Schäfer (Member of the German Center for Lung Research), Alexander Dietrich (Member of the German Center for Lung Research) & Thomas Gudermann (Member of the German Center for Lung Research)

  4. Institut für Pharmakologie und Toxikologie der Bundeswehr, Neuherbergstrasse 11, München, 80937, Germany

    Dirk Steinritz

Authors
  1. Thomas Büch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eva Schäfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dirk Steinritz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexander Dietrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Gudermann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Gudermann .

Editor information

Editors and Affiliations

  1. Dept. of Cell. and Molecular Medicine Lab. of Ion Channel Research, KU Leuven, Leuven, Belgium

    Bernd Nilius

  2. Deptartment of Neurobiology Biomedical Science Tower 3, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Susan G. Amara

  3. Walther-Straub-Institut für Pharmakologi, Ludwig-Maximilians-Universität München Medizinische Fakultät, München, Germany

    Thomas Gudermann

  4. MPI für Biophysikalische Chemie Abt. Neurobiologie, Göttingen, Germany

    Reinhard Jahn

  5. Zytopathologie, Universität Marburg Inst. Zytobiologie und, Marburg, Germany

    Roland Lill

  6. Abteilung II, Max-Planck-Institut für Herz- und Lungen, Bad Nauheim, Germany

    Stefan Offermanns

  7. Cardiff University School of Biosciences, Cardiff, United Kingdom

    Ole H. Petersen

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Büch, T., Schäfer, E., Steinritz, D., Dietrich, A., Gudermann, T. (2013). Chemosensory TRP Channels in the Respiratory Tract: Role in Toxic Lung Injury and Potential as “Sweet Spots” for Targeted Therapies. In: Nilius, B., et al. Reviews of Physiology, Biochemistry and Pharmacology, Vol. 165. Reviews of Physiology, Biochemistry and Pharmacology, vol 165. Springer, Cham. https://doi.org/10.1007/112_2012_10

Download citation

Publish with us

Policies and ethics

Search

Navigation