Role of TRPV1 and P2X receptors in the activation of lung vagal C-fiber afferents by inhaled cigarette smoke in rats

Weng,Wen-Hui; Hsu,Chun-Chun; Chiang,Ling-Ling; Lin,Yi-Jiun  Peter; Lin,You  Shuei; Su,Chien-Ling

doi:10.3892/mmr.2013.1300

Role of TRPV1 and P2X receptors in the activation of lung vagal C-fiber afferents by inhaled cigarette smoke in rats

Authors:
- Wen-Hui Weng
- Chun-Chun Hsu
- Ling-Ling Chiang
- Yi-Jiun Peter Lin
- You Shuei Lin
- Chien-Ling Su
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Affiliations: Department of Chemical Engineering Biotechnology, National Taipei University Of Technology, Taipei, Taiwan, R.O.C., Department Of Physiology, Taipei Medical University, Taipei, Taiwan, R.O.C., School Of Respiratory Therapy, Taipei Medical University, Taipei, Taiwan, R.O.C., Department Of Mechanical Engineering, National Taiwan University Of Science And Technology, Taipei, Taiwan, R.O.C.
Published online on: January 30, 2013 https://doi.org/10.3892/mmr.2013.1300
Pages: 1300-1304

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Abstract

Inhaled cigarette smoke (CS) triggers airway reflexes that are thought to result from the activation of lung vagal C-fiber afferents (LVCAs) via the action of reactive oxygen species in rats. We investigated the role of transient receptor potential vanilloid 1 (TRPV1) and P2X receptors in LVCA activation. Activities of LVCAs were recorded in anesthetized and artificially ventilated rats. Airway challenge of CS produced a concentration-dependent fiber stimulation. Pretreatment with dimethylthiourea [DMTU; a scavenger of hydroxyl radical (•OH)], capsazepine (CPZ; a TRPV1 receptor antagonist) and iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (iso-PPADS; a P2X receptor antagonist) separately reduced the fiber responses by 64, 40 and 44%, respectively, whereas pretreatment with hexamethonium (a nicotinic acetylcholine receptor antagonist) failed to alter the response. A combination of CPZ and iso-PPADS exerted a greater inhibitory effect compared with the effect of either single pretreatment. However, a combination of DMTU, CPZ and iso-PPADS did not further reduce the fiber response compared with the combined effect of CPZ and iso-PPADS. It was concluded that both TRPV1 and P2X receptors, but not nicotinic acetylcholine receptors, participate in the stimulation of LVCAs by inhaled CS, possibly through the action of •OH.

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1	Lee LY, Burki NK, Gerhardstein DC, Gu Q, Kou YR and Xu J: Airway irritation and cough evoked by inhaled cigarette smoke: role of neuronal nicotinic acetylcholine receptors. Pulm Pharmacol Ther. 20:355–364. 2007. View Article : Google Scholar : PubMed/NCBI
2	Chung KF and Pavord ID: Prevalence, pathogenesis and causes of chronic cough. Lancet. 371:1364–1374. 2008. View Article : Google Scholar : PubMed/NCBI
3	Lee LY and Gu Q: Cough sensors. IV. Nicotinic membrane receptors on cough sensors. Pharmacology and Therapeutics of Cough. Chung KF and Widdicombe J: Springer; New York, NY: pp. 77–98. 2009, View Article : Google Scholar : PubMed/NCBI
4	Yu J: Airway receptors and their reflex function-invited article. Adv Exp Med Biol. 648:411–420. 2009. View Article : Google Scholar : PubMed/NCBI
5	Lin YS, Hsu CC, Bien MY, Hsu HC, Wing HT and Kou YR: 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. 2010. View Article : Google Scholar : PubMed/NCBI
6	Ruan T, Lin YS, Lin KS and Kou YR: Mediator mechanisms involved in TRPV1 and P2X receptor-mediated, ROS-evoked bradypneic reflex in anesthetized rats. J Appl Physiol. 101:644–654. 2006. View Article : Google Scholar : PubMed/NCBI
7	Ruan T, Lin YS, Lin KS and Kou YR: Sensory transduction of pulmonary reactive oxygen species by capsaicin-sensitive vagal lung afferent fibres in rats. J Physiol. 565:563–578. 2005. View Article : Google Scholar : PubMed/NCBI
8	Bessac BF and Jordt SE: Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. Physiology (Bethesda). 23:360–370. 2008. View Article : Google Scholar : PubMed/NCBI
9	Bessac BF, Sivula M, von Hehn CA, Escalera J, Cohn L and Jordt SE: TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest. 118:1899–1910. 2008. View Article : Google Scholar : PubMed/NCBI
10	Taylor-Clark TE, McAlexander MA, Nassenstein C, Sheardown SA, Wilson S, Thornton J, Carr MJ and Undem BJ: 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. 2008. View Article : Google Scholar : PubMed/NCBI
11	Borgerding M and Klus H: Analysis of complex mixtures - cigarette smoke. Exp Toxicol Pathol. 57(Suppl 1): 43–73. 2005. View Article : Google Scholar : PubMed/NCBI
12	Lee LY, Kou YR, Frazier DT, Beck ER, Pisarri TE, Coleridge HM and Coleridge JC: Stimulation of vagal pulmonary C-fibers by a single breath of cigarette smoke in dogs. J Appl Physiol. 66:2032–2038. 1989.PubMed/NCBI
13	Xu J, Yang W, Zhang G, Gu Q and Lee LY: Calcium transient evoked by nicotine in isolated rat vagal pulmonary sensory neurons. Am J Physiol Lung Cell Mol Physiol. 292:L54–L61. 2007. View Article : Google Scholar : PubMed/NCBI
14	Pryor WA: Oxy-radicals and related species: their formation, lifetimes, and reactions. Annu Rev Physiol. 48:657–667. 1986. View Article : Google Scholar : PubMed/NCBI
15	Lin YS and Lee LY: Stimulation of pulmonary vagal C-fibres by anandamide in anaesthetized rats: role of vanilloid type 1 receptors. J Physiol. 539:947–955. 2002. View Article : Google Scholar : PubMed/NCBI
16	Lei YH, Barnes PJ and Rogers DF: Involvement of hydroxyl radicals in neurogenic airway plasma exudation and bronchoconstriction in guinea-pigs in vivo. Br J Pharmacol. 117:449–454. 1996. View Article : Google Scholar : PubMed/NCBI
17	Lee LY: Inhibitory effect of gas phase cigarette smoke on breathing: role of hydroxyl radical. Respir Physiol. 82:227–238. 1990. View Article : Google Scholar : PubMed/NCBI
18	Coggins CRE, Fouillet XL, Lam R and Morgan KT: Cigarette smoke induced pathology of the rat respiratory tract: a comparison of the effects of the particulate and vapor phases. Toxicology. 16:83–101. 1980. View Article : Google Scholar : PubMed/NCBI
19	Pankow JF: A consideration of the role of gas/particle partitioning in the deposition of nicotine and other tobacco smoke compounds in the respiratory tract. Chem Res Toxicol. 14:1465–1481. 2001. View Article : Google Scholar : PubMed/NCBI