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Liviero, Filippo (2019) La modulazione dei canali transient receptor potential v1 e a1 con prostaglandina-e2e bradichinina è associata adaumento della risposta tussigena alla capsaicina ed a variazionidella regolazioneautonomica del ritmo cardiaco in soggetti sani. [Ph.D. thesis]

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Abstract (italian or english)

BACKGROUND:
Vi sono evidenze in modelli animali che l’inalazione di particolato fine (PM), attivi i recettori polmonari TRPV1 e TRPA1 e attraverso una modulazione del sistema nervoso centrale possa influenzare la regolazione autonomica dell'attività cardiaca. Questa ipotetica via neurogena, potrebbe essere responsabile degli effetti cardiovascolari avversi osservati in soggetti suscettibili dopo esposizioni acute a PM.
OBIETTIVI:
Verificare che l'attività di TRPV1 e TRPA1 può essere modulata in vivo dall’inalazione di prostaglandina-E2 (PGE2) e bradichinina (BK), e che i cambiamenti nell'attività dei canali TRP interferiscano con la regolazione autonomica del ritmo cardiaco nell’uomo. In un gruppo di volontari sani abbiamo valutato:
1. la risposta tussigena alla capsaicina (CPS) ed alla cinnamaldeide (CMA), agonisti esogeni rispettivamente dei canali TRPV1 e TRPA1, somministrati per via inalatoria prima e dopo l'inalazione di PGE2 e BK, agonisti endogeni in grado di attivare in vitro i canali TRP;
2. la variabilità della frequenza cardiaca (HRV) al momento della modulazione dei canali TRP con PGE2 e BK.
È stato inoltre verificato:
3. il meccanismo molecolare della modulazione del canale TRPV1 in vitro su cellule HeLa trasfettate con la forma wild-type del TRPV1;
4. se la presenza di polimorfismi funzionali (SNPs) di TRPV1 spieghi la variabilità della risposta tussigena alla CPS e se modifichi la risposta tussigena alla modulazione dei canali TRP con PGE2 e BK.
MATERIALI E METODI:
1. Sono stati reclutati 20 volontari sani, 17 dei quali hanno effettuato l’inalazione di PGE2 e BK o diluente, in modo randomizzato e in doppio cieco. Subito dopo, ogni soggetto è stato sottoposto al test di stimolazione specifica del recettore TRPV1 con CPS e TRPA1 con CMA.
2. In 12 dei volontari sani arruolati è stata misurata la HRV tramite la registrazione dell’elettrocardiogramma (ECG), avvenuta dopo l’inalazione di diluente, PGE2 e BK. Abbiamo analizzato tre variabili delle componenti spettrali nel dominio della frequenza che rappresentano indici di modulazione simpatica, vagale e del bilancio simpatico-vagale.
3. Abbiamo monitorato la funzionalità del canale TRPV1 misurando la concentrazione di [Ca2+] nelle cellule HeLa dopo trattamento con CPS e CMA. Abbiamo trasfettato le cellule HeLa con il canale umano TRPV1 per misurarne la funzionalità, dopo il pre-trattamento con dosi crescenti di PGE2, BK o particolato di scarico diesel (DEP) e successiva stimolazione con CPS.
4. Tutti i volontari sono stati caratterizzati per la risposta tussigena alla CPS. Abbiamo analizzato il DNA di ciascuno per caratterizzare sei SNPs di TRPV1.
RISULTATI:
1. L'inalazione di PGE2 e BK ha determinato un aumento significativo della risposta tussigena indotta dalla CPS, indicando un aumento di sensibilità del TRPV1. La modulazione del TRPA1 ha mostrato cambiamenti inconsistenti della risposta tussigena indotta dalla CMA.
2. L'inalazione di PGE2 e BK ha modificato significativamente l’HRV comportando uno sbilanciamento della regolazione autonomica del ritmo cardiaco a favore del sistema simpatico rispetto al vagale.
3. Il pretrattamento con PGE2 o BK delle cellule HeLa che esprimono il TRPV1, non ha modificato le risposte cellulari indotte da CPS, dimostrando come nel nostro modello sperimentale, questi due mediatori non sensibilizzino direttamente il canale TRPV1. Il trattamento con il DEP ha aumentato significativamente le risposte cellulari mediate da CPS, indicando che TRPV1 è direttamente sensibilizzato dal particolato.
4. La variabilità della risposta tussigena alla CPS tra soggetti sani è spiegata da molteplici SNPs del canale TRPV1. Il contributo maggiore alla sensibilità in termini di risposta tussigena alla CPS in vivo è dovuto alla presenza di quattro SNPs combinati: I315M; I585V; T469I; P91S.

Questi dati supportano l’ipotesi che l’inalazione di PM, interferendo con la funzione dei TRP, induca effetti cardiovascolari acuti in soggetti suscettibili.


Abstract (a different language)

BACKGROUND
There is evidence in animal models, that particulate (PM) inhalation, activates TRPV-1 and TRPA-1 pulmonary receptors and may change the autonomic regulation of cardiac activity, through a modulation of afferent signals in the central nervous system. This hypothetical neurogenic pathway could explain the adverse cardiovascular effects observed in susceptible subjects after acute PM exposures.
OBJECTIVES
The aim of the study was to verify that the activity of TRPV-1 and TRPA-1 can be modulated in vivo by inhaled stimuli and that changes in TRP channels activity modify the autonomic regulation of heart rhythm. To do this we evaluated in a group of healthy volunteers:
1. Cough response to capsaicin (CPS) and cinnmaldeide (CMA), exogenous agonists of TRPV-1 and TRPA-1 channels, before and after inhalation of PGE2 and BK, endogenous mediators that activate TRP channels in vitro;
2. Heart rate variability (HRV) after modulation of TRP channels with PGE2 and BK.
We also evaluated:
3. The molecular mechanism of TRPV-1 channel modulation in vitro, on HeLa cells transfected with the TRPV-1 wild-type;
4. Whether presence of functional polymorphisms (SNPs) of TRPV-1 explains the variability of cough response to CPS and whether it modifies cough response to the modulation of TRP channels with PGE2 and BK.
METHODS
1. 20 healthy volunteers were recruited. 17 performed PGE2 and BK or diluent inhalation, in a randomized double-blind fashion. Immediately after inhalation of the modulators, the sensitivity of TRPV-1 to CPS and of TRPA-1 to CMA was assessed with cough challenge.
2. Heart rate variability (HRV) was tested in 12 of the enrolled healthy volunteers recording the electrocardiogram (ECG) after inhalation of diluent, PGE2 and BK. We analyzed the variables of spectral components in the frequency domain, that represent indexes of sympathetic, vagal and sympathetic-vagal balance.
3. Functional properties of TRPV-1 channel were evaluated measuring [Ca2 +] in HeLa cells after treatment with CPS and CMA. HeLa cells were transfected with the TRPV-1 human channel. [Ca2 +] in HeLa cells was measured after pre-treatment with increasing doses of PGE2, BK or diesel exhaust particulate matter (DEP) followed by CPS stimulation.
4. All volunteers were characterized according to cough response to the CPS. We analyzed the DNA of each subjects to assess the presence of six functional polymorphisms (SNPs) of TRPV-1.
RESULTS
1. Inhalation of PGE2 and BK is associated with a significant increase of cough response induced by CPS, while inconsistent changes after stimulation of TRPA-1 with CMA were detected.
2. Inhalation of PGE2 and BK significantly modifies HRV, leading to an imbalance of the autonomic regulation of heart rhythm. In particular we detected an upregulation of the sympathetic system and a downregulation of the vagal system.
3. Pretreatment with PGE2 or BK of HeLa cells expressing TRPV-1 did not modify CPS-induced cellular responses, demonstrating that in our experimental model, these two mediators do not directly sensitize the TRPV-1 channel. Treatment with DEP significantly increased TRPV-1-mediated cellular responses, indicating that it is directly sensitized by particulate matter.
4. We demonstrated that the variability of cough response to CPS between healthy subjects is partially explained by multiple SNPs of the TRPV-1 channel. The major contribution to sensitivity in terms of cough response to CPS in vivo is due to the combination of four SNPs: I315M; I585V; T469I; P91S. However, the modulation of TRPV-1 was irrespective of the presence of SNPs.
These data support the hypothesis that PM inhalation, interfering with the function of TRPs, induces acute cardiovascular effects in susceptible subjects.

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EPrint type:Ph.D. thesis
Tutor:Maestrelli, Piero
Ph.D. course:Ciclo 32 > Corsi 32 > SCIENZE FARMACOLOGICHE > FARMACOLOGIA, TOSSICOLOGIA E TERAPIA
Data di deposito della tesi:09 January 2020
Anno di Pubblicazione:01 December 2019
More information:CORSO DI DOTTORATO IN SCIENZE FARMACOLOGICHE CURRICULUM TOSSICOLOGIA E TERAPIA CICLO XXXII
Key Words:CANALI TRP; TOSSE; HRV; SNPs
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/44 Medicina del lavoro
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari
Dipartimenti > Dipartimento di Scienze del Farmaco
Codice ID:12811
Depositato il:25 Jan 2021 12:25
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BIBLIOGRAFIA Cerca con Google

Adcock, J.J., Birrell, M.A., Maher, S.A., Bonvini, S.J., Dubuis, E., Wortley, M.A., Baker, K.E., Belvisi, M.G. Making Sense Of Sensory Nerves: An In Vivo Characterisation Of Aδ- And C-Fibres Innervating Guinea-Pig Airways [Abstract]. Am J Respir Crit Care Med, 2014. 189: p. A3969. Cerca con Google

Ahluwalia, A., & Perretti, M. (1999). B1 receptors as a new inflammatory target. Could this B the 1? Trends Pharmacol Sci, 20(3), 100-104. Cerca con Google

Andre, E., Campi, B., Materazzi, S., Trevisani, M., Amadesi, S., Massi, D., Creminon, C., Vaksman, N., Nassini, R., Civelli, M., Baraldi, P.G., Poole, D.P., Bunnett, N.W., 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. Cerca con Google

Andre, E., Gatti, R., Trevisani, M., Preti, D., Baraldi, P.G., 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. Cerca con Google

Aramori, I., Zenkoh, J., Morikawa, N., O'Donnell, N., Asano, M., Nakamura, K., Iwami, M., Kojo, H., & Notsu, Y. (1997). Novel subtype-selective nonpeptide bradykinin receptor antagonists FR167344 and FR173657. Mol Pharmacol, 51(2), 171-176. Cerca con Google

Ayari, I., Fedeli, U., Saguem, S., Hidar, S., Khlifi, S., & Pavanello, S. (2013). Role of CYP1A2 polymorphisms in breast cancer risk in women. Mol Med Rep, 7(1), 280-286. Cerca con Google

Bandell, M., Story, G.M., Hwang, S.W., Viswanath, V., Eid, S.R., Petrus, M.J., Earley, T.J., & Patapoutian, A. (2004). Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron, 41(6), 849-857. Cerca con Google

Bang, S., Kim, K.Y., Yoo, S., Kim, Y.G., & Hwang, S.W. (2007). Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation. Eur J Neurosci, 26(9), 2516-2523. Cerca con Google

Barnes, N.C., Piper, P.J., & Costello, J.F. (1984). Comparative effects of inhaled leukotriene C4, leukotriene D4, and histamine in normal human subjects. Thorax, 39(7), 500-504. Cerca con Google

Bastien, L., Sawyer, N., Grygorczyk, R., Metters, K.M., & Adam, M. (1994). Cloning, functional expression, and characterization of the human prostaglandin E2 receptor EP2 subtype. J Biol Chem, 269(16), 11873-11877. Cerca con Google

Bautista, D.M., Jordt, S.E., Nikai, T., Tsuruda, P.R., Read, A.J., Poblete, J., Yamoah, E.N., Basbaum, A.I., & Julius, D. (2006). TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell, 124(6), 1269-1282. Cerca con Google

Belvisi, M.G., Birrell, M.A., Khalid, S., Wortley, M.A., Dockry, R., Coote, J., Holt, K., Dubuis, E., Kelsall, A., Maher, S.A., Bonvini, S., Woodcock, A., & Smith, J.A. (2016). Neurophenotypes in Airway Diseases. Insights from Translational Cough Studies. Am J Respir Crit Care Med, 193(12), 1364-1372. Cerca con Google

Bergren, D.R. (1997). Sensory receptor activation by mediators of defense reflexes in guinea-pig lungs. Respir Physiol, 108(3), 195-204. Cerca con Google

Bianchi, B.R., El Kouhen, R., Chen, J., & Puttfarcken, P.S. (2010). Binding of [(3)H]A-778317 to native transient receptor potential vanilloid-1 (TRPV1) channels in rat dorsal root ganglia and spinal cord. Eur J Pharmacol, 633(1-3), 15-23. Cerca con Google

Birrell, M.A., Belvisi, M.G., Grace, M., Sadofsky, L., Faruqi, S., Hele, D.J., Maher, S.A., Freund-Michel, V., & Morice, A.H. (2009). TRPA1 agonists evoke coughing in guinea pig and human volunteers. Am J Respir Crit Care Med, 180(11), 1042-1047. Cerca con Google

Birring, S.S., Fleming, T., Matos, S., Raj, A.A., Evans, D.H., & Pavord, I.D. (2008). The Leicester Cough Monitor: preliminary validation of an automated cough detection system in chronic cough. Eur Respir J, 31(5), 1013-1018. Cerca con Google

Brito, R., Sheth, S., Mukherjea, D., Rybak, L.P., & Ramkumar, V. (2014). TRPV1: A Potential Drug Target for Treating Various Diseases. Cells, 3(2), 517-545. Cerca con Google

Brook, R.D., Rajagopalan, S., Pope, C.A., 3rd, Brook, J.R., Bhatnagar, A., Diez-Roux, A.V., Holguin, F., Hong, Y., Luepker, R.V., Mittleman, M.A., Peters, A., Siscovick, D., Smith, S.C., Jr., Whitsel, L., & Kaufman, J.D. (2010). Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation, 121(21), 2331-2378. Cerca con Google

Burki, N.K., Dale, W.J., & Lee, L.Y. (2005). Intravenous adenosine and dyspnea in humans. J Appl Physiol (1985), 98(1), 180-185. Cerca con Google

Canning, B.J., Reynolds, S.M., & Mazzone, S.B. (2001). Multiple mechanisms of reflex bronchospasm in guinea pigs. J Appl Physiol (1985), 91(6), 2642-2653. Cerca con Google

Canning, B.J., Mazzone, S.B., Meeker, S.N., Mori, N., Reynolds, S.M., & Undem, B.J. (2004). Identification of the tracheal and laryngeal afferent neurones mediating cough in anaesthetized guinea-pigs. J Physiol, 557(Pt 2), 543-558. Cerca con Google

Canning, B.J., Farmer, D.G., & Mori, N. (2006). Mechanistic studies of acid-evoked coughing in anesthetized guinea pigs. Am J Physiol Regul Integr Comp Physiol, 291(2), R454-463. Cerca con Google

Canning, B.J., Mori, N., & Mazzone, S.B. (2006). Vagal afferent nerves regulating the cough reflex. Respir Physiol Neurobiol, 152(3), 223-242. Cerca con Google

Canning, B.J., & Chou, Y.L. (2009). Cough sensors. I. Physiological and pharmacological properties of the afferent nerves regulating cough. Handb Exp Pharmacol(187), 23-47. Cerca con Google

Canning, B.J. (2011). Functional implications of the multiple afferent pathways regulating cough. Pulm Pharmacol Ther, 24(3), 295-299. Cerca con Google

Cantero-Recasens, G., Gonzalez, J.R., Fandos, C., Duran-Tauleria, E., Smit, L.A., Kauffmann, F., Anto, J.M., & Valverde, M.A. (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(36), 27532-27535. Cerca con Google

Carr, M.J., Kollarik, M., Meeker, S.N., & Undem, B.J. (2003). A role for TRPV1 in bradykinin-induced excitation of vagal airway afferent nerve terminals. J Pharmacol Exp Ther, 304(3), 1275-1279. Cerca con Google

Caterina, M.J., Schumacher, M.A., Tominaga, M., Rosen, T.A., Levine, J.D., & Julius, D. (1997). The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature, 389(6653), 816-824. Cerca con Google

Choudry, N.B., Fuller, R.W., & Pride, N.B. (1989). Sensitivity of the human cough reflex: effect of inflammatory mediators prostaglandin E2, bradykinin, and histamine. Am Rev Respir Dis, 140(1), 137-141. Cerca con Google

Chuaychoo, B., Lee, M.G., Kollarik, M., & Undem, B.J. (2005). Effect of 5-hydroxytryptamine on vagal C-fiber subtypes in guinea pig lungs. Pulm Pharmacol Ther, 18(4), 269-276. Cerca con Google

Chuaychoo, B., Lee, M.G., Kollarik, M., Pullmann, R., Jr., & Undem, B.J. (2006). Evidence for both adenosine A1 and A2A receptors activating single vagal sensory C-fibres in guinea pig lungs. J Physiol, 575(Pt 2), 481-490. Cerca con Google

Chung, K.F., & Widdicombe, J.G. (2009). Cough: setting the scene. Handb Exp Pharmacol(187), 1-21. Cerca con Google

Clapham, D.E., Julius, D., Montell, C., & Schultz, G. (2005). International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacol Rev, 57(4), 427-450. Cerca con Google

Coleridge, H.M., Coleridge, J.C., & Roberts, A.M. (1983). Rapid shallow breathing evoked by selective stimulation of airway C fibres in dogs. J Physiol, 340, 415-433. Cerca con Google

Couture, R., Harrisson, M., Vianna, R.M., & Cloutier, F. (2001). Kinin receptors in pain and inflammation. Eur J Pharmacol, 429(1-3), 161-176. Cerca con Google

Deering-Rice, C.E., Romero, E.G., Shapiro, D., Hughen, R.W., Light, A.R., Yost, G.S., Veranth, J.M., & Reilly, C.A. (2011). Electrophilic components of diesel exhaust particles (DEP) activate transient receptor potential ankyrin-1 (TRPA1): a probable mechanism of acute pulmonary toxicity for DEP. Chem Res Toxicol, 24(6), 950-959. Cerca con Google

Deering-Rice, C.E., Johansen, M.E., Roberts, J.K., Thomas, K.C., Romero, E.G., Lee, J., Yost, G.S., Veranth, J.M., & Reilly, C.A. (2012). Transient receptor potential vanilloid-1 (TRPV1) is a mediator of lung toxicity for coal fly ash particulate material. Mol Pharmacol, 81(3), 411-419. Cerca con Google

Deering-Rice, C.E., Stockmann, C., Romero, E.G., Lu, Z., Shapiro, D., Stone, B.L., Fassl, B., Nkoy, F., Uchida, D.A., Ward, R.M., Veranth, J.M., & Reilly, C.A. (2016). Characterization of Transient Receptor Potential Vanilloid-1 (TRPV1) Variant Activation by Coal Fly Ash Particles and Associations with Altered Transient Receptor Potential Ankyrin-1 (TRPA1) Expression and Asthma. J Biol Chem, 291(48), 24866-24879. Cerca con Google

Devos, F.C., Boonen, B., Alpizar, Y.A., Maes, T., Hox, V., Seys, S., Pollaris, L., Liston, A., Nemery, B., Talavera, K., Hoet, P.H., & Vanoirbeek, J.A. (2016). Neuro-immune interactions in chemical-induced airway hyperreactivity. Eur Respir J, 48(2), 380-392. Cerca con Google

Dicpinigaitis, P.V., Rhoton, W.A., Bhat, R., & Negassa, A. (2012). Investigation of the urge-to-cough sensation in healthy volunteers. Respirology, 17(2), 337-341. Cerca con Google

Ferrer-Montiel, A., Fernandez-Carvajal, A., Planells-Cases, R., Fernandez-Ballester, G., Gonzalez-Ros, J.M., Messeguer, A., & Gonzalez-Muniz, R. (2012). Advances in modulating thermosensory TRP channels. Expert Opin Ther Pat, 22(9), 999-1017. Cerca con Google

Folino, A.F., Scapellato, M.L., Canova, C., Maestrelli, P., Bertorelli, G., Simonato, L., Iliceto, S., & Lotti, M. (2009). Individual exposure to particulate matter and the short-term arrhythmic and autonomic profiles in patients with myocardial infarction. Eur Heart J, 30(13), 1614-1620. Cerca con Google

Folino, F., Buja, G., Zanotto, G., Marras, E., Allocca, G., Vaccari, D., Gasparini, G., Bertaglia, E., Zoppo, F., Calzolari, V., Suh, R.N., Ignatiuk, B., Lanera, C., Benassi, A., Gregori, D., & Iliceto, S. (2017). Association between air pollution and ventricular arrhythmias in high-risk patients (ARIA study): a multicentre longitudinal study. Lancet Planet Health, 1(2), e58-e64. Cerca con Google

Forstenpointner, J., Forster, M., May, D., Hofschulte, F., Cascorbi, I., Wasner, G., Gierthmuhlen, J., & Baron, R. (2017). Short Report: TRPV1-polymorphism 1911 A>G alters capsaicin-induced sensory changes in healthy subjects. PLoS One, 12(8), e0183322. Cerca con Google

Fujimura, M., Sakamoto, S., Kamio, Y., & Matsuda, T. (1992). Effects of methacholine induced bronchoconstriction and procaterol induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid. Thorax, 47(6), 441-445. Cerca con Google

Gees, M., Colsoul, B., & Nilius, B. (2010). The role of transient receptor potential cation channels in Ca2+ signaling. Cold Spring Harb Perspect Biol, 2(10), a003962. Cerca con Google

Geppetti, P., Materazzi, S., & Nicoletti, P. (2006). The transient receptor potential vanilloid 1: role in airway inflammation and disease. Eur J Pharmacol, 533(1-3), 207-214. Cerca con Google

Ghelfi, E., Rhoden, C.R., Wellenius, G.A., Lawrence, J., & Gonzalez-Flecha, B. (2008). Cardiac oxidative stress and electrophysiological changes in rats exposed to concentrated ambient particles are mediated by TRP-dependent pulmonary reflexes. Toxicol Sci, 102(2), 328-336. Cerca con Google

Ghelfi, E., Wellenius, G.A., Lawrence, J., Millet, E., & Gonzalez-Flecha, B. (2008). Cardiac oxidative stress and dysfunction by fine concentrated ambient particles (CAPs) are mediated by angiotensin-II. Inhal Toxicol, 22(11), 963-972. Cerca con Google

Grace, M., Birrell, M.A., Dubuis, E., Maher, S.A., & Belvisi, M.G. (2012). Transient receptor potential channels mediate the tussive response to prostaglandin E2 and bradykinin. Thorax, 67(10), 891-900. Cerca con Google

Grace, M.S., & Belvisi, M.G. (2011). TRPA1 receptors in cough. Pulm Pharmacol Ther, 24(3), 286-288. Cerca con Google

Grace, M.S., Dubuis, E., Birrell, M.A., & Belvisi, M.G. (2012). TRP channel antagonists as potential antitussives. Lung, 190(1), 11-15. Cerca con Google

Grace, M.S., Baxter, M., Dubuis, E., Birrell, M.A., & Belvisi, M.G. (2013). Transient receptor potential (TRP) channels in the airway: role in airway disease. Br J Pharmacol, 171(10), 2593-2607. Cerca con Google

Grace, M.S., Dubuis, E., Birrell, M.A., & Belvisi, M.G. (2013). Pre-clinical studies in cough research: role of Transient Receptor Potential (TRP) channels. Pulm Pharmacol Ther, 26(5), 498-507. Cerca con Google

Granatiero, V., Patron, M., Tosatto, A., Merli, G., & Rizzuto, R. (2014). Using targeted variants of aequorin to measure Ca2+ levels in intracellular organelles. Cold Spring Harb Protoc, 2014(1), 86-93. Cerca con Google

Groneberg, D.A., Niimi, A., Dinh, Q.T., Cosio, B., Hew, M., Fischer, A., & Chung, K.F. (2004). Increased expression of transient receptor potential vanilloid-1 in airway nerves of chronic cough. Am J Respir Crit Care Med, 170(12), 1276-1280. Cerca con Google

Haque, R.A., Usmani, O.S., & Barnes, P.J. (2005). Chronic idiopathic cough: a discrete clinical entity? Chest, 127(5), 1710-1713. Cerca con Google

Harle, A.S., Blackhall, F.H., Smith, J.A., & Molassiotis, A. (2012). Understanding cough and its management in lung cancer. Curr Opin Support Palliat Care, 6(2), 153-162. Cerca con Google

Hartert, T.V., Dworski, R.T., Mellen, B.G., Oates, J.A., Murray, J.J., & Sheller, J.R. (2000). Prostaglandin E(2) decreases allergen-stimulated release of prostaglandin D(2) in airways of subjects with asthma. Am J Respir Crit Care Med, 162(2 Pt 1), 637-640. Cerca con Google

Ho, C.Y., Gu, Q., Lin, Y.S., & Lee, L.Y. (2001). Sensitivity of vagal afferent endings to chemical irritants in the rat lung. Respir Physiol, 127(2-3), 113-124. Cerca con Google

Holguin, F., Tellez-Rojo, M.M., Hernandez, M., Cortez, M., Chow, J.C., Watson, J.G., Mannino, D., & Romieu, I. (2003). Air pollution and heart rate variability among the elderly in Mexico City. Epidemiology, 14(5), 521-527. Cerca con Google

Jang, Y., Lee, Y., Kim, S.M., Yang, Y.D., Jung, J., & Oh, U. (2012). Quantitative analysis of TRP channel genes in mouse organs. Arch Pharm Res, 35(10), 1823-1830. Cerca con Google

Jia, Y., McLeod, R.L., Wang, X., Parra, L.E., Egan, R.W., & Hey, J.A. (2002). Anandamide induces cough in conscious guinea-pigs through VR1 receptors. Br J Pharmacol, 137(6), 831-836. Cerca con Google

Kagaya, M., Lamb, J., Robbins, J., Page, C.P., & Spina, D. (2002). Characterization of the anandamide induced depolarization of guinea-pig isolated vagus nerve. Br J Pharmacol, 137(1), 39-48. Cerca con Google

Kajekar, R., Proud, D., Myers, A.C., Meeker, S.N., & Undem, B.J. (1999). Characterization of vagal afferent subtypes stimulated by bradykinin in guinea pig trachea. J Pharmacol Exp Ther, 289(2), 682-687. Cerca con Google

Kharitonov, S.A., Sapienza, M.M., Chung, K.F., & Barnes, P.J. (1999). Prostaglandins mediate bradykinin-induced reduction of exhaled nitric oxide in asthma. Eur Respir J, 14(5), 1023-1027. Cerca con Google

Koizumi, K., Terui, N., & Kollai, M. (1985). Effect of cardiac vagal and sympathetic nerve activity on heart rate in rhythmic fluctuations. J Auton Nerv Syst, 12(2-3), 251-259. Cerca con Google

Kollarik, M., & Undem, B.J. (2002). Mechanisms of acid-induced activation of airway afferent nerve fibres in guinea-pig. J Physiol, 543(Pt 2), 591-600. Cerca con Google

Kollarik, M., & Undem, B.J. (2004). Activation of bronchopulmonary vagal afferent nerves with bradykinin, acid and vanilloid receptor agonists in wild-type and TRPV1-/- mice. J Physiol, 555(Pt 1), 115-123. Cerca con Google

Kwong, K., Carr, M.J., Gibbard, A., Savage, T.J., Singh, K., Jing, J., Meeker, S., & Undem, B.J. (2008). Voltage-gated sodium channels in nociceptive versus non-nociceptive nodose vagal sensory neurons innervating guinea pig lungs. J Physiol, 586(5), 1321-1336. Cerca con Google

Lalloo, U.G., Fox, A.J., Belvisi, M.G., Chung, K.F., & Barnes, P.J. (1995). Capsazepine inhibits cough induced by capsaicin and citric acid but not by hypertonic saline in guinea pigs. J Appl Physiol (1985), 79(4), 1082-1087. Cerca con Google

Lee, L.Y., & Pisarri, T.E. (2001). Afferent properties and reflex functions of bronchopulmonary C-fibers. Respir Physiol, 125(1-2), 47-65. Cerca con Google

Lee, L.Y., & Widdicombe, J.G. (2001). Modulation of airway sensitivity to inhaled irritants: role of inflammatory mediators. Environ Health Perspect, 109 Suppl 4, 585-589. Cerca con Google

Lee, L.Y., & Gu, Q. (2009). Role of TRPV1 in inflammation-induced airway hypersensitivity. Curr Opin Pharmacol, 9(3), 243-249. Cerca con Google

Lee, M.G., Macglashan, D.W., Jr., & Undem, B.J. (2005). Role of chloride channels in bradykinin-induced guinea pig airway vagal C-fibre activation. J Physiol, 566(Pt 1), 205-212. Cerca con Google

Leech, J., Mazzone, S.B., & Farrell, M.J. (2012). The effect of placebo conditioning on capsaicin-evoked urge to cough. Chest, 142(4), 951-957. Cerca con Google

Leech, J., Mazzone, S.B., & Farrell, M.J. (2013). Brain activity associated with placebo suppression of the urge-to-cough in humans. Am J Respir Crit Care Med, 188(9), 1069-1075. Cerca con Google

Macpherson, L.J., Geierstanger, B.H., Viswanath, V., Bandell, M., Eid, S.R., Hwang, S., & Patapoutian, A. (2005). The pungency of garlic: activation of TRPA1 and TRPV1 in response to allicin. Curr Biol, 15(10), 929-934. Cerca con Google

Maher, S.A., Birrell, M.A., & Belvisi, M.G. (2009). Prostaglandin E2 mediates cough via the EP3 receptor: implications for future disease therapy. Am J Respir Crit Care Med, 180(10), 923-928. Cerca con Google

Malik et al. (1996). Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation, 93(5), 1043-1065. Cerca con Google

Mamet, J., Baron, A., Lazdunski, M., & Voilley, N. (2002). Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels. J Neurosci, 22(24), 10662-10670. Cerca con Google

Marsden, P.A., Smith, J.A., Kelsall, A.A., Owen, E., Naylor, J.R., Webster, D., Sumner, H., Alam, U., McGuinness, K., & Woodcock, A.A. (2008). A comparison of objective and subjective measures of cough in asthma. J Allergy Clin Immunol, 122(5), 903-907. Cerca con Google

Mazzone, S.B., Mori, N., & Canning, B.J. (2005). Synergistic interactions between airway afferent nerve subtypes regulating the cough reflex in guinea-pigs. J Physiol, 569(Pt 2), 559-573. Cerca con Google

Mazzone, S.B., & McGovern, A.E. (2006). Na+-K+-2Cl- cotransporters and Cl- channels regulate citric acid cough in guinea pigs. J Appl Physiol (1985), 101(2), 635-643. Cerca con Google

Mazzone, S.B., McLennan, L., McGovern, A.E., Egan, G.F., & Farrell, M.J. (2007). Representation of capsaicin-evoked urge-to-cough in the human brain using functional magnetic resonance imaging. Am J Respir Crit Care Med, 176(4), 327-332. Cerca con Google

Mazzone, S.B., Reynolds, S.M., Mori, N., Kollarik, M., Farmer, D.G., Myers, A.C., & Canning, B.J. (2009). Selective expression of a sodium pump isozyme by cough receptors and evidence for its essential role in regulating cough. J Neurosci, 29(43), 13662-13671. Cerca con Google

McLeod, R.L., Fernandez, X., Correll, C.C., Phelps, T.P., Jia, Y., Wang, X., & Hey, J.A. (2006). TRPV1 antagonists attenuate antigen-provoked cough in ovalbumin sensitized guinea pigs. Cough, 2, 10. Cerca con Google

Midgren, B., Hansson, L., Karlsson, J.A., Simonsson, B.G., & Persson, C.G. (1992). Capsaicin-induced cough in humans. Am Rev Respir Dis, 146(2), 347-351. Cerca con Google

Moak, J.P., Goldstein, D.S., Eldadah, B.A., Saleem, A., Holmes, C., Pechnik, S., & Sharabi, Y. (2009). Supine low-frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation. Heart Rhythm, 4(12), 1523-1529. Cerca con Google

Montell, C. (2005). The TRP superfamily of cation channels. Sci STKE, 2005(272), re3. Cerca con Google

Morice, A.H., Higgins, K.S., & Yeo, W.W. (1992). Adaptation of cough reflex with different types of stimulation. Eur Respir J, 5(7), 841-847. Cerca con Google

Morice, A.H. (2001). Research methods in human respiratory pharmacology. Br J Clin Pharmacol, 51(4), 287. Cerca con Google

Morice, A.H., McGarvey, L., & Pavord, I. (2006). Recommendations for the management of cough in adults. Thorax, 61 Suppl 1, i1-24. Cerca con Google

Morice, A.H., Fontana, G.A., Belvisi, M.G., Birring, S.S., Chung, K.F., Dicpinigaitis, P.V., Kastelik, J.A., McGarvey, L.P., Smith, J.A., Tatar, M., & Widdicombe, J. (2007). ERS guidelines on the assessment of cough. Eur Respir J, 29(6), 1256-1276. Cerca con Google

Mustafic, H., Jabre, P., Caussin, C., Murad, M.H., Escolano, S., Tafflet, M., Perier, M.C., Marijon, E., Vernerey, D., Empana, J.P., & Jouven, X. (2012). Main air pollutants and myocardial infarction: a systematic review and meta-analysis. Jama, 307(7), 713-721. Cerca con Google

Nassenstein, C., Kwong, K., Taylor-Clark, T., Kollarik, M., Macglashan, D.M., Braun, A., & Undem, B.J. (2008). Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs. J Physiol, 586(6), 1595-1604. Cerca con Google

Nishino, T., Tagaito, Y., & Isono, S. (1996). Cough and other reflexes on irritation of airway mucosa in man. Pulm Pharmacol, 9(5-6), 285-292. Cerca con Google

Pavanello, S., Angelici, L., Hoxha, M., Cantone, L., Campisi, M., Tirelli, A.S., Vigna, L., Pesatori, A.C., & Bollati, V. (2018). Sterol 27-Hydroxylase Polymorphism Significantly Associates With Shorter Telomere, Higher Cardiovascular and Type-2 Diabetes Risk in Obese Subjects. Front Endocrinol (Lausanne), 9, 309. Cerca con Google

Peters, A., von Klot, S., Heier, M., Trentinaglia, I., Hormann, A., Wichmann, H.E., & Lowel, H. (2004). Exposure to traffic and the onset of myocardial infarction. N Engl J Med, 351(17), 1721-1730. Cerca con Google

Pope, C.A., 3rd, & Dockery, D.W. (2006). Health effects of fine particulate air pollution: lines that connect. J Air Waste Manag Assoc, 56(6), 709-742. Cerca con Google

Premkumar, L.S., & Ahern, G.P. (2000). Induction of vanilloid receptor channel activity by protein kinase C. Nature, 408(6815), 985-990. Cerca con Google

Rahman, F., Pechnik, S., Gross, D., Sewell, L., & Goldstein, D.S. (2011). Low frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation. Clin Auton Res, 21(3), 133-141. Cerca con Google

Ramsey, I.S., Delling, M., & Clapham, D.E. (2006). An introduction to TRP channels. Annu Rev Physiol, 68, 619-647. Cerca con Google

Rech, J.C., Eckert, W.A., Maher, M.P., Banke, T., Bhattacharya, A., & Wickenden, A.D. (2010). Recent advances in the biology and medicinal chemistry of TRPA1. Future Med Chem, 2(5), 843-858. Cerca con Google

Reilly, C.A., Taylor, J.L., Lanza, D.L., Carr, B.A., Crouch, D.J., & Yost, G.S. (2003). Capsaicinoids cause inflammation and epithelial cell death through activation of vanilloid receptors. Toxicol Sci, 73(1), 170-181. Cerca con Google

Rhoden, C.R., Wellenius, G.A., Ghelfi, E., Lawrence, J., & Gonzalez-Flecha, B. (2005). PM-induced cardiac oxidative stress and dysfunction are mediated by autonomic stimulation. Biochim Biophys Acta, 1725(3), 305-313. Cerca con Google

Rizzuto, R., Simpson, A.W., Brini, M., & Pozzan, T. (1992). Rapid changes of mitochondrial Ca2+ revealed by specifically targeted recombinant aequorin. Nature, 358(6384), 325-327. Cerca con Google

Robertson, S., Thomson, A.L., Carter, R., Stott, H.R., Shaw, C.A., Hadoke, P.W., Newby, D.E., Miller, M.R., & Gray, G.A. (2014). Pulmonary diesel particulate increases susceptibility to myocardial ischemia/reperfusion injury via activation of sensory TRPV1 and beta1 adrenoreceptors. Part Fibre Toxicol, 11, 12. Cerca con Google

Robinson, R.K., Birrell, M.A., Adcock, J.J., Wortley, M.A., Dubuis, E.D., Chen, S., McGilvery, C.M., Hu, S., Shaffer, M.S.P., Bonvini, S.J., Maher, S.A., Mudway, I.S., Porter, A.E., Carlsten, C., Tetley, T.D., & Belvisi, M.G. (2018). Mechanistic link between diesel exhaust particles and respiratory reflexes. J Allergy Clin Immunol, 141(3), 1074-1084 e1079. Cerca con Google

Sadofsky, L.R., Cantero-Recasens, G., Wright, C., Valverde, M.A., & Morice, A.H. (2017). TRPV1 polymorphisms influence capsaicin cough sensitivity in men. J Thorac Dis, 9(3), 839-840. Cerca con Google

Schappert, S.M., & Burt, C.W. (2006). Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 2001-02. Vital Health Stat 13(159), 1-66. Cerca con Google

Schelegle, E.S., & Green, J.F. (2001). An overview of the anatomy and physiology of slowly adapting pulmonary stretch receptors. Respir Physiol, 125(1-2), 17-31. Cerca con Google

Shapiro, D., Deering-Rice, C.E., Romero, E.G., Hughen, R.W., Light, A.R., Veranth, J.M., & Reilly, C.A. (2013). Activation of transient receptor potential ankyrin-1 (TRPA1) in lung cells by wood smoke particulate material. Chem Res Toxicol, 26(5), 750-758. Cerca con Google

Shimomura, O., Johnson, F.H., & Saiga, Y. (1963). Microdetermination of Calcium by Aequorin Luminescence. Science, 140(3573), 1339-1340. Cerca con Google

Shin, J., Cho, H., Hwang, S.W., Jung, J., Shin, C.Y., Lee, S.Y., Kim, S.H., Lee, M.G., Choi, Y.H., Kim, J., Haber, N.A., Reichling, D.B., Khasar, S., Levine, J.D., & Oh, U. (2002). Bradykinin-12-lipoxygenase-VR1 signaling pathway for inflammatory hyperalgesia. Proc Natl Acad Sci U S A, 99(15), 10150-10155. Cerca con Google

Smit, L.A., Kogevinas, M., Anto, J.M., Bouzigon, E., Gonzalez, J.R., Le Moual, N., Kromhout, H., Carsin, A.E., Pin, I., Jarvis, D., Vermeulen, R., Janson, C., Heinrich, J., Gut, I., Lathrop, M., Valverde, M.A., Demenais, F., & Kauffmann, F. (2012). Transient receptor potential genes, smoking, occupational exposures and cough in adults. Respir Res, 13, 26. Cerca con Google

Smith, J., Owen, E., Earis, J., & Woodcock, A. (2006). Cough in COPD: correlation of objective monitoring with cough challenge and subjective assessments. Chest, 130(2), 379-385. Cerca con Google

Stone, R.A., Worsdell, Y.M., Fuller, R.W., & Barnes, P.J. (1993). Effects of 5-hydroxytryptamine and 5-hydroxytryptophan infusion on the human cough reflex. J Appl Physiol (1985), 74(1), 396-401. Cerca con Google

Sugiura, T., Tominaga, M., Katsuya, H., & Mizumura, K. (2002). Bradykinin lowers the threshold temperature for heat activation of vanilloid receptor 1. J Neurophysiol, 88(1), 544-548. Cerca con Google

Sun, Q., Hong, X., & Wold, L.E. (2010). Cardiovascular effects of ambient particulate air pollution exposure. Circulation, 121(25), 2755-2765. Cerca con Google

Szallasi, A., & Blumberg, P.M. (1999). Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev, 51(2), 159-212. Cerca con Google

Tanraev, A.D. (1975). [Helminthological evaluation of the use of manure in dairy complexes]. Veterinariia(6), 42-44. Cerca con Google

Tarvainen, M.P., Niskanen, J.P., Lipponen, J.A., Ranta-Aho, P.O., & Karjalainen, P.A. (2014). Kubios HRV--heart rate variability analysis software. Comput Methods Programs Biomed, 113(1), 210-220. Cerca con Google

Tatar, M., Webber, S.E., & Widdicombe, J.G. (1988). Lung C-fibre receptor activation and defensive reflexes in anaesthetized cats. J Physiol, 402, 411-420. Cerca con Google

Tatar, M., Sant'Ambrogio, G., & Sant'Ambrogio, F.B. (1994). Laryngeal and tracheobronchial cough in anesthetized dogs. J Appl Physiol (1985), 76(6), 2672-2679. Cerca con Google

Trevisani, M., Siemens, J., Materazzi, S., Bautista, D.M., Nassini, R., Campi, B., Imamachi, N., Andre, E., Patacchini, R., Cottrell, G.S., Gatti, R., Basbaum, A.I., Bunnett, N.W., 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 U S A, 104(33), 13519-13524. Cerca con Google

Undem, B.J., & Weinreich, D. (1993). Electrophysiological properties and chemosensitivity of guinea pig nodose ganglion neurons in vitro. J Auton Nerv Syst, 44(1), 17-33. Cerca con Google

Undem, B.J., Chuaychoo, B., Lee, M.G., Weinreich, D., Myers, A.C., & Kollarik, M. (2004). Subtypes of vagal afferent C-fibres in guinea-pig lungs. J Physiol, 556(Pt 3), 905-917. Cerca con Google

van Esch, A.A., Lamberts, M.P., te Morsche, R.H., van Oijen, M.G., Jansen, J.B., & Drenth, J.P. (2009). Polymorphisms in gene encoding TRPV1-receptor involved in pain perception are unrelated to chronic pancreatitis. BMC Gastroenterol, 9, 97. Cerca con Google

Watanabe, N., Horie, S., Michael, G.J., Keir, S., Spina, D., Page, C.P., & Priestley, J.V. (2006). Immunohistochemical co-localization of transient receptor potential vanilloid (TRPV)1 and sensory neuropeptides in the guinea-pig respiratory system. Neuroscience, 141(3), 1533-1543. Cerca con Google

Widdicombe, J. (2003). Functional morphology and physiology of pulmonary rapidly adapting receptors (RARs). Anat Rec A Discov Mol Cell Evol Biol, 270(1), 2-10. Cerca con Google

Widdicombe, J.G. (1954a). Receptors in the trachea and bronchi of the cat. J Physiol, 123(1), 71-104. Cerca con Google

Widdicombe, J.G. (1954b). Respiratory reflexes from the trachea and bronchi of the cat. J Physiol, 123(1), 55-70. Cerca con Google

Widdicombe, J.G. (1954c). Respiratory reflexes excited by inflation of the lungs. J Physiol, 123(1), 105-115. Cerca con Google

Widdicombe, J.G. (1998). Afferent receptors in the airways and cough. Respir Physiol, 114(1), 5-15. Cerca con Google

Xu, H., Tian, W., Fu, Y., Oyama, T.T., Anderson, S., & Cohen, D.M. (2007). Functional effects of nonsynonymous polymorphisms in the human TRPV1 gene. Am J Physiol Renal Physiol, 293(6), F1865-1876. Cerca con Google

Zhang, G., Lin, R.L., Wiggers, M., Snow, D.M., & Lee, L.Y. (2008). Altered expression of TRPV1 and sensitivity to capsaicin in pulmonary myelinated afferents following chronic airway inflammation in the rat. J Physiol, 586(23), 5771-5786. Cerca con Google

Zhou, Y., Sun, B., Li, Q., Luo, P., Dong, L., & Rong, W. (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(3), 327-332. Cerca con Google

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