Nicotine activates and up-regulates nicotinic acetylcholine receptors in bronchial epithelial cells

Wen Fu Xiao, Jon Lindstrom, Eliot R. Spindel

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Prenatal nicotine exposure impairs normal lung development and leads to diminished pulmonary function after birth. Previous work from our laboratory has demonstrated that nicotine alters lung development by affecting a nonneuronal cholinergic autocrine loop that is expressed in lung. Bronchial epithelial cells (BECs) express choline acetyltransferase, the choline high-affinity transporter and nicotinic acetylcholine (ACh) receptor (nAChR) subunits. We now demonstrate through a combination of morphological and electrophysiological techniques that nicotine affects this autocrine loop by up-regulating and activating cholinergic signaling. RT-PCR showed the expression of α3, α4, α7, α9, α10, β2, and β4 nAChR mRNAs in rhesus monkey lung and cultured BECs. The expression of α7, α4, and β2 nAChR was confirmed by immunofluorescence in the cultured BECs and lung. The electrophysiological characteristics of nAChR in BECs were determined using whole-cell patch-clamp on cultured BECs. Both ACh and nicotine evoked an inward current, with a rapid desensitizing current. Nicotine induced inward currents in a concentration-dependent manner, with an EC50 of 26.7 μM. Nicotine-induced currents were reversibly blocked by the nicotinic antagonists, mecamylamine, dihydro-β-erythroidine, and methyllcaconitine. Incubation of BECs with 1 μM nicotine for 48 hours enhanced nicotine-induced currents by roughly 26%. The protein tyrosine phosphorylation inhibitor, genistein, increased nicotine-induced currents by 58% and enhanced methyllcaconitine- sensitive currents (α7 nAChR activities) 2.3-fold, whereas the protein tyrosine phosphatase inhibitor, pervanadate, decreased the effects of nicotine. These results demonstrate that chronic nicotine exposure upregulates nAChR activity in developing lung, and that nAChR activity can be further modified by tyrosine phosphorylation.

Original languageEnglish (US)
Pages (from-to)93-99
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Issue number1
StatePublished - Jul 1 2009


  • Bronchial epithelial cells
  • Electrophysiology
  • Lung
  • Nicotine
  • Nicotinic acetylcholine receptors

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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