title: Role of TRPV1 and P2X receptors in the activation of lung vagal C-fiber afferents by inhaled cigarette smoke in rats.
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.
authors: Department of Chemical Engineering Biotechnology, National Taipei University Of Technology, Taipei, Taiwan, R.O.C.
authors: Wen-Hui
authors: WH
authors: Weng
authors: Chun-Chun
authors: CC
authors: Hsu
authors: Ling-Ling
authors: LL
authors: Chiang
authors: Yi-Jiun Peter
authors: YJ
authors: Lin
authors: You Shuei
authors: YS
authors: Lin
authors: Chien-Ling
authors: CL
authors: Su
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D017665:Hydroxyl Radical; D011732:Pyridoxal Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism; D058469:Receptors, Purinergic P2X / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects; D050916:TRPV Cation Channels / Q000378:metabolism*; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D017382:Reactive Oxygen Species; D011978:Receptors, Nicotinic; D058469:Receptors, Purinergic P2X; D012906:Smoke; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D017665:Hydroxyl Radical; D011732:Pyridoxal Phosphate; C038983:1,3-dimethylthiourea; D013890:Thiourea; C071423:capsazepine; D002211:Capsaicin