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Reflex bronchoconstriction evoked by inhaled nicotine aerosol in guinea pigs: role of the nicotinic acetylcholine receptor
Author(s) -
Lin RueiLung,
Khosravi Mehdi,
Xu Fadi,
Lee LuYuan
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.726.7
Subject(s) - bronchoconstriction , nicotine , chemistry , acetylcholine , atropine , reflex , nicotinic agonist , anesthesia , pharmacology , stimulation , endocrinology , medicine , receptor , airway , biochemistry
We have previously reported that stimulation of vagal bronchopulmonary C‐fibers by nicotine via its action on neuronal nicotinic acetylcholine receptor (NnAChR) is primarily responsible for the acute bronchoconstriction evoked by inhaled cigarette smoke. Recent studies have reported that nicotine at high concentrations can also activate the transient receptor potential ankyrin 1 receptor (TRPA1) expressed in these sensory nerves. This study was carried out to investigate the mechanisms involved in the bronchoconstrictive effect of inhaled nicotine, and the relative roles of NnAChR and TRPA1 in this effect. Guinea pigs were anesthetized and mechanically ventilated; nicotine aerosol (2% solution; 1 × V T ) was diluted by air to 2 × V T and delivered directly into the lung via trachea tube. Our results showed: 1) Delivery of one breath of nicotine aerosol immediately triggered a pronounced airway constriction; the increase in airway resistance (R aw ) reached a peak of 588 ± 205 % in 10–40 sec, which gradually returned to baseline after 1–5 min. The response was reproducible in the same animal tested 20 min later. 2) Challenge with aerosolized alkaline solution of the same pH as that in the nicotine solution (10.5) did not cause any change in R aw . 3) Pretreatment with atropine (0.1 mg/kg; i.v.) and mecamylamine (Mec; an antagonist of NnAChR) (2%; 4 breaths of aerosol) almost completely abolished the nicotine‐induced bronchoconstriction: ΔR aw was reduced by 83.1 ± 8.2 % and 92.5 ± 1.9 %, respectively. The Mec pretreatment did not block the bronchoconstriction and bradycardia generated by electrical stimulation of the distal end of one sectioned vagus nerve, indicating its minimal systemic effects. 4) Pretreatment with HC‐030031 (0.5 mg/kg; i.v.), a selective TRPA1 antagonist, abolished the bronchoconstriction induced by allyl isothiocyanate (1.7 mg/kg, i.v.), a TRPA1 agonist, but did not render any attenuation of the nicotine‐evoked bronchoconstriction. In conclusion, inhalation of a single puff of nicotine aerosol evoked acute bronchoconstriction mediated through the cholinergic reflex pathway, which was triggered by activation of NnAChR located in airway sensory nerves. In contrast, TRPA1 receptor did not play a significant role in this response. Support or Funding Information Supported by NIH grants HL96914, HL107462 and UL1TR001998