title: Hydrogen sulfide induces hypersensitivity of rat capsaicin-sensitive lung vagal neurons: role of TRPA1 receptors.
abstract: The sensitization of capsaicin-sensitive lung vagal (CSLV) afferents by inflammatory mediators is important in the development of airway hypersensitivity. Hydrogen sulfide (H2S) is an endogenous mediator inducing hyperalgesia through transient receptor potential ankyrin 1 (TRPA1) receptors located on nociceptors. We conducted this study to determine whether H2S elevates the sensitivity of rat CSLV afferents. In anesthetized, artificially ventilated rats, the inhalation of aerosolized sodium hydrosulfide (NaHS, a H2S donor) caused no significant changes in the baseline activity of CSLV afferents. However, the afferent responses to right atrial injection of capsaicin or phenylbiguanide and to lung inflation were all markedly potentiated after NaHS inhalation. By contrast, the inhalation of its vehicle or NaOH (with a similar pH to NaHS) failed to enhance the afferent responses. Additionally, the potentiating effect on the afferent responses was found in rats inhaling L-cysteine (a substrate of H2S synthase) that slowly releases H2S. The potentiating effect of NaHS on the sensitivity of CSLV afferents was completely blocked by pretreatment of HC-030031 (a TRPA1 receptor antagonist) but was unaffected by its vehicle. In isolated rat CSLV neurons, the perfusion of NaHS alone did not influence the intracellular Ca(2+) concentration but markedly potentiated the Ca(2+) transients evoked by capsaicin. The NaHS-caused effect was totally abolished by HC-030031 pretreatment. These results suggest that H2S induces a nonspecific sensitizing effect on CSLV fibers to both chemical and mechanical stimulation in rat lungs, which appears mediated through an action on the TRPA1 receptors expressed on the nerve endings of CSLV afferents.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan;
authors.forename: Chun-Chun
authors.initials: CC
authors.lastname: Hsu
authors.forename: Ruei-Lung
authors.initials: RL
authors.lastname: Lin
authors.forename: Lu-Yuan
authors.initials: LY
authors.lastname: Lee
authors.forename: You Shuei
authors.initials: YS
authors.lastname: Lin
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D002478:Cells, Cultured; D003545:Cysteine / Q000008:administration & dosage; D008168:Lung / Q000294:innervation*; D008297:Male; D040542:Mechanotransduction, Cellular; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D011312:Pressure; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000008:administration & dosage* / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D014630:Vagus Nerve / Q000187:drug effects* / Q000378:metabolism
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D000336:Aerosols; D011687:Purines; D013440:Sulfides; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; C025451:sodium bisulfide; D003545:Cysteine; D002211:Capsaicin
keywords: H2S; TRPA1 receptors; afferent sensitization; lung; lung vagal C fibers