Premium
Impact of Developmental Nicotine Exposure on Cholinergic Airway Signaling
Author(s) -
Rivera Benjamin D,
Borrero Nathan G,
Cross Seres J.B.,
Fregosi Ralph F,
Boitano Scott
Publication year - 2019
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.2019.33.1_supplement.lb612
Subject(s) - nicotine , cholinergic , nicotinic agonist , acetylcholine receptor , nicotinic acetylcholine receptor , endocrinology , medicine , amiloride , pharmacology , receptor , chemistry , organic chemistry , sodium
In 2014, 8.4% of US women reported smoking during pregnancy. Conservatively, this translates into approximately 360,000 smoke‐exposed infants born in 2015 in the United States. Fetal nicotine exposure alters cholinergic signaling through activation of Nicotinic Acetylcholine Receptors (nAChRs) in the developing lung and nervous system. Altered expression of nAChRs can persist and result in lasting changes in lung function. The impact on airway nAChRs, which can influence ion transport to control the airway surface liquid layer and mucociliary clearance, remains poorly defined. Here we begin to discern the impact of an acute nicotine challenge on airway epithelial signaling by evaluating the tracheae of animals exposed to nicotine in utero and after birth (developmental nicotine exposure, DNE) and controls (saline exposed sham). Tracheae were excised from neonate rats between post‐natal days 7 – 12 and were mounted in Ussing Chambers to measure transtracheal resistance (TTR) and short circuit current (Isc) in response to nicotine. The resting TTR in DNE animals trended lower than that in sham‐treated animals. Additionally, it was found that compared to sham, tracheae from DNE‐treated animals displayed significantly larger peak Isc in response to nicotine. Isc experiments of whole neonate tracheae in the presence of epithelial Na + channel (ENaC), Ca‐induced Cl Channel (CaCC) or CFTR Channel inhibitors (amiloride, DIDS and CFTRinh‐172, respectively) suggest that the bulk of the peak Isc is mediated by CaCC secretion in response to the Ca 2+ influx triggered by activation of nAChRs. Preliminary experiments to evaluate changes in nAChR subunit expression between DNE and control animals using mRNA extraction and qPCR suggest altered subunit expression in the DNE‐treated animals. In summary, we report the first Ussing Chamber recordings from rat neonate tracheae and demonstrate significant changes in Isc following DNE. These data highlight the potential physiological changes of early life exposure to nicotine, independent of cigarette smoke. Support or Funding Information National Institutes of Health Grants: NIEHS/SBRPP ES094940 (SB), NIEHS/EHS‐TRUE ES025494 (NGB), NICHD HD071302 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .