Activations of TRPA1 and P2X receptors are important in ROS-Mediated stimulation of capsaicin-Sensitive lung vagal afferents by cigarette smoke in rats

You-Shuei Lin, Chun-Chun Hsu, Mauo-Ying Bien, Hui-Chi Hsu, Hsu-Ting Weng, Yu-Ru Kou

Research output: Contribution to journalArticle

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Abstract

Capsaicin-sensitive lung vagal afferents (CSLVAs) are important in detecting pulmonary reactive oxygen species (ROS). We investigated the mechanisms underlying the stimulation of CSLVAs by inhaled cigarette smoke (CS) in 216 anesthetized rats. In spontaneously breathing rats, CS evoked a CSLVA-mediated reflex bradypnea that was prevented by N-acetyl-L-cysteine (NAC; an antioxidant), HC-030031 [a transient receptor potential ankyrin 1 (TRPA1) receptor antagonist], and isopyridoxalphosphate-6-azophenyl-2′,5′- disulfonate (iso-PPADS; a P2X receptor antagonist). In paralyzed, artificially ventilated rats, CS evoked an increase in CSLVA fiber activity (AFA) that was abolished by NAC and was attenuated by HC-030031, iso-PPADS, indomethacin. (Indo; a cyclooxygenase inhibitor), and a combination of apyrase and adenosine deaminase (ADA) (ATP scavengers); the response to CS was reduced to 11.7 ± 4.0%, 39.5 ± 10.0%, 52.9 ± 14.4%, 68.7 ± 10.1%, and 47.2 ± 12.9% of control, respectively. The suppressive effect on this afferent response was not improved by a combination of HC030031 and Indo (AFA = 39.5 ± 10.1% of control) compared with that induced by HC-030031 alone. In contrast, the suppressive effect was enhanced by a combination of HC-030031 and apyrase+ADA (AFA = 5.3 ± 4.9% of control) or a combination, of iso-PPADS and Indo (AFA = 23.3 ± 7.7% of control) compared with that induced by HC-030031 alone or iso-PPADS alone. This afferent response was not altered by the vehicles for these drugs. These results suggest that activations of TRPA1 receptors by cyclooxygenase metabolites and P2X receptors by ATP are both necessary for the ROS-mediated stimulation of CSLVA fibers by CS in rats.

Original languageEnglish
Pages (from-to)1293-1303
Number of pages11
JournalJournal of Applied Physiology
Volume108
Issue number5
DOIs
Publication statusPublished - May 2010

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Ankyrins
Capsaicin
Smoke
Tobacco Products
Reactive Oxygen Species
Lung
Apyrase
Adenosine Deaminase
Purinergic P2 Receptors
Cyclooxygenase 1
Cyclooxygenase Inhibitors
Acetylcysteine
Indomethacin
Reflex
2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
Respiration
Antioxidants
Adenosine Triphosphate
pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid
Pharmaceutical Preparations

Keywords

  • Lung vagal C fibers
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Activations of TRPA1 and P2X receptors are important in ROS-Mediated stimulation of capsaicin-Sensitive lung vagal afferents by cigarette smoke in rats. / Lin, You-Shuei; Hsu, Chun-Chun; Bien, Mauo-Ying; Hsu, Hui-Chi; Weng, Hsu-Ting; Kou, Yu-Ru.

In: Journal of Applied Physiology, Vol. 108, No. 5, 05.2010, p. 1293-1303.

Research output: Contribution to journalArticle

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abstract = "Capsaicin-sensitive lung vagal afferents (CSLVAs) are important in detecting pulmonary reactive oxygen species (ROS). We investigated the mechanisms underlying the stimulation of CSLVAs by inhaled cigarette smoke (CS) in 216 anesthetized rats. In spontaneously breathing rats, CS evoked a CSLVA-mediated reflex bradypnea that was prevented by N-acetyl-L-cysteine (NAC; an antioxidant), HC-030031 [a transient receptor potential ankyrin 1 (TRPA1) receptor antagonist], and isopyridoxalphosphate-6-azophenyl-2′,5′- disulfonate (iso-PPADS; a P2X receptor antagonist). In paralyzed, artificially ventilated rats, CS evoked an increase in CSLVA fiber activity (AFA) that was abolished by NAC and was attenuated by HC-030031, iso-PPADS, indomethacin. (Indo; a cyclooxygenase inhibitor), and a combination of apyrase and adenosine deaminase (ADA) (ATP scavengers); the response to CS was reduced to 11.7 ± 4.0{\%}, 39.5 ± 10.0{\%}, 52.9 ± 14.4{\%}, 68.7 ± 10.1{\%}, and 47.2 ± 12.9{\%} of control, respectively. The suppressive effect on this afferent response was not improved by a combination of HC030031 and Indo (AFA = 39.5 ± 10.1{\%} of control) compared with that induced by HC-030031 alone. In contrast, the suppressive effect was enhanced by a combination of HC-030031 and apyrase+ADA (AFA = 5.3 ± 4.9{\%} of control) or a combination, of iso-PPADS and Indo (AFA = 23.3 ± 7.7{\%} of control) compared with that induced by HC-030031 alone or iso-PPADS alone. This afferent response was not altered by the vehicles for these drugs. These results suggest that activations of TRPA1 receptors by cyclooxygenase metabolites and P2X receptors by ATP are both necessary for the ROS-mediated stimulation of CSLVA fibers by CS in rats.",
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N2 - Capsaicin-sensitive lung vagal afferents (CSLVAs) are important in detecting pulmonary reactive oxygen species (ROS). We investigated the mechanisms underlying the stimulation of CSLVAs by inhaled cigarette smoke (CS) in 216 anesthetized rats. In spontaneously breathing rats, CS evoked a CSLVA-mediated reflex bradypnea that was prevented by N-acetyl-L-cysteine (NAC; an antioxidant), HC-030031 [a transient receptor potential ankyrin 1 (TRPA1) receptor antagonist], and isopyridoxalphosphate-6-azophenyl-2′,5′- disulfonate (iso-PPADS; a P2X receptor antagonist). In paralyzed, artificially ventilated rats, CS evoked an increase in CSLVA fiber activity (AFA) that was abolished by NAC and was attenuated by HC-030031, iso-PPADS, indomethacin. (Indo; a cyclooxygenase inhibitor), and a combination of apyrase and adenosine deaminase (ADA) (ATP scavengers); the response to CS was reduced to 11.7 ± 4.0%, 39.5 ± 10.0%, 52.9 ± 14.4%, 68.7 ± 10.1%, and 47.2 ± 12.9% of control, respectively. The suppressive effect on this afferent response was not improved by a combination of HC030031 and Indo (AFA = 39.5 ± 10.1% of control) compared with that induced by HC-030031 alone. In contrast, the suppressive effect was enhanced by a combination of HC-030031 and apyrase+ADA (AFA = 5.3 ± 4.9% of control) or a combination, of iso-PPADS and Indo (AFA = 23.3 ± 7.7% of control) compared with that induced by HC-030031 alone or iso-PPADS alone. This afferent response was not altered by the vehicles for these drugs. These results suggest that activations of TRPA1 receptors by cyclooxygenase metabolites and P2X receptors by ATP are both necessary for the ROS-mediated stimulation of CSLVA fibers by CS in rats.

AB - Capsaicin-sensitive lung vagal afferents (CSLVAs) are important in detecting pulmonary reactive oxygen species (ROS). We investigated the mechanisms underlying the stimulation of CSLVAs by inhaled cigarette smoke (CS) in 216 anesthetized rats. In spontaneously breathing rats, CS evoked a CSLVA-mediated reflex bradypnea that was prevented by N-acetyl-L-cysteine (NAC; an antioxidant), HC-030031 [a transient receptor potential ankyrin 1 (TRPA1) receptor antagonist], and isopyridoxalphosphate-6-azophenyl-2′,5′- disulfonate (iso-PPADS; a P2X receptor antagonist). In paralyzed, artificially ventilated rats, CS evoked an increase in CSLVA fiber activity (AFA) that was abolished by NAC and was attenuated by HC-030031, iso-PPADS, indomethacin. (Indo; a cyclooxygenase inhibitor), and a combination of apyrase and adenosine deaminase (ADA) (ATP scavengers); the response to CS was reduced to 11.7 ± 4.0%, 39.5 ± 10.0%, 52.9 ± 14.4%, 68.7 ± 10.1%, and 47.2 ± 12.9% of control, respectively. The suppressive effect on this afferent response was not improved by a combination of HC030031 and Indo (AFA = 39.5 ± 10.1% of control) compared with that induced by HC-030031 alone. In contrast, the suppressive effect was enhanced by a combination of HC-030031 and apyrase+ADA (AFA = 5.3 ± 4.9% of control) or a combination, of iso-PPADS and Indo (AFA = 23.3 ± 7.7% of control) compared with that induced by HC-030031 alone or iso-PPADS alone. This afferent response was not altered by the vehicles for these drugs. These results suggest that activations of TRPA1 receptors by cyclooxygenase metabolites and P2X receptors by ATP are both necessary for the ROS-mediated stimulation of CSLVA fibers by CS in rats.

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