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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 (1985). 2010 May; 108(5):1293-303.JA

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 iso-pyridoxalphosphate-6-azophenyl-2',5'-disulfonate (iso-PPADS; a P2X receptor antagonist). In paralyzed, artificially ventilated rats, CS evoked an increase in CSLVA fiber activity (DeltaFA) 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 HC-030031 and Indo (DeltaFA=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 (DeltaFA=5.3+/-4.9% of control) or a combination of iso-PPADS and Indo (DeltaFA=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.

Authors+Show Affiliations

Graduate Institute of Medical Sciences, Department of Physiology, School of Respiratory Therapy, College of Medicine, Taipei Medical University, and Neuroscience Research Center, Department of Respiratory Therapy, Taipei Medical University Hospital, Taipei, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20167675

Citation

Lin, You Shuei, et al. "Activations of TRPA1 and P2X Receptors Are Important in ROS-mediated Stimulation of Capsaicin-sensitive Lung Vagal Afferents By Cigarette Smoke in Rats." Journal of Applied Physiology (Bethesda, Md. : 1985), vol. 108, no. 5, 2010, pp. 1293-303.
Lin YS, Hsu CC, Bien MY, et al. 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 (1985). 2010;108(5):1293-303.
Lin, Y. S., Hsu, C. C., Bien, M. Y., Hsu, H. C., Weng, H. T., & Kou, Y. R. (2010). Activations of TRPA1 and P2X receptors are important in ROS-mediated stimulation of capsaicin-sensitive lung vagal afferents by cigarette smoke in rats. Journal of Applied Physiology (Bethesda, Md. : 1985), 108(5), 1293-303. https://doi.org/10.1152/japplphysiol.01048.2009
Lin YS, et al. 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 (1985). 2010;108(5):1293-303. PubMed PMID: 20167675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activations of TRPA1 and P2X receptors are important in ROS-mediated stimulation of capsaicin-sensitive lung vagal afferents by cigarette smoke in rats. AU - Lin,You Shuei, AU - Hsu,Chun-Chun, AU - Bien,Mauo-Ying, AU - Hsu,Hui-Chi, AU - Weng,Hsu-Ting, AU - Kou,Yu Ru, Y1 - 2010/02/18/ PY - 2010/2/20/entrez PY - 2010/2/20/pubmed PY - 2010/8/13/medline SP - 1293 EP - 303 JF - Journal of applied physiology (Bethesda, Md. : 1985) JO - J Appl Physiol (1985) VL - 108 IS - 5 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 iso-pyridoxalphosphate-6-azophenyl-2',5'-disulfonate (iso-PPADS; a P2X receptor antagonist). In paralyzed, artificially ventilated rats, CS evoked an increase in CSLVA fiber activity (DeltaFA) 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 HC-030031 and Indo (DeltaFA=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 (DeltaFA=5.3+/-4.9% of control) or a combination of iso-PPADS and Indo (DeltaFA=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. SN - 1522-1601 UR - https://www.unboundmedicine.com/medline/citation/20167675/Activations_of_TRPA1_and_P2X_receptors_are_important_in_ROS_mediated_stimulation_of_capsaicin_sensitive_lung_vagal_afferents_by_cigarette_smoke_in_rats_ L2 - https://journals.physiology.org/doi/10.1152/japplphysiol.01048.2009?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -