Effects of Perinatal Nicotine Exposure on Cholinergic Signaling in the Airway Epithelium

Abstract

Up to 20% of pregnant women in the USA smoke or use nicotine delivery devices (e‐cigarettes, water pipes, nicotine patches or gum). While addictive, many believe nicotine to be otherwise safe, causing the use of nicotine delivery devices to double between 2008–2012. However, there is growing evidence that nicotine can alter development of the lungs and airways, as well as pulmonary immune function and brainstem neurons that control breathing and heart rate. In this study, we propose to test the hypothesis that in utero exposure to nicotine leads to alterations in cholinergic signaling in the airway that are evident at birth and persist into adulthood. Importantly, dysfunction of acetylcholine (ACh) signaling in the airway epithelium can result in compromised airway surface liquid and subsequent loss of innate immune function in the airways. This signaling is mediated primarily by muscarinic acetylcholine receptors (mAChRs) and nicotinic acetylcholine receptors (nAChRs), both of which may be affected by developmental nicotine exposure. We have used rat neonate tracheal mounts and primary cultured rodent airway epithelium in Ussing Chamber studies to evaluate airway epithelial cholinergic signaling in animals with and without developmental nicotine exposure. Initial results show that transtracheal resistance (TTR), transepithelial resistances (TER), and short circuit current (Isc) responses to apical application of ACh are not altered by nicotine exposure. However, airway epithelial signaling is dominated by mAChRs‐dependent signaling. When preparations are exposed to nicotine, unexposed rat trachea and primary mouse cultures demonstrate limited, but clear responses. These responses appear to be altered in animals exposed to nicotine in utero. Our data suggest that perinatal nicotine exposure adversely affects the development of cholinergic signaling in the airway epithelium.Support or Funding Information1R25ES025494NIEHS/SBRPP ES04940