Prolongation of bronchopulmonary C-fiber-mediated apnea by prenatal nicotinic exposure in rat pups: role of 5-HT3 receptors

FASEB J. 2019 Oct;33(10):10731-10741. doi: 10.1096/fj.201900279RR. Epub 2019 Jun 27.


Prenatal nicotinic exposure (PNE) reportedly sensitizes bronchopulmonary C-fibers (PCFs) and prolongs PCF-mediated apnea in rat pups, contributing to the pathogenesis of sudden infant death syndrome. Serotonin, or 5-hydroxytryptamine (5-HT), induces apnea via acting on 5-HT receptor 3 (5-HT3R) in PCFs, and among the 5-HT3R subunits, 5-HT3B is responsible for shortening the decay time of 5-HT3R-mediated currents. We examined whether PNE would promote pulmonary 5-HT secretion and prolong the apnea mediated by 5-HT3Rs in PCFs via affecting the 5-HT3B subunit. To this end, the following variables were compared between the control and PNE rat pups: 1) the 5-HT content in bronchoalveolar lavage fluid, 2) the apneic response to the right atrial bolus injection of phenylbiguanide (a 5-HT3R agonist) before and after PCF inactivation, 3) 5-HT3R currents and the stimulus threshold of the action currents of vagal pulmonary C-neurons, and 4) the immunoreactivity (IR) and mRNA expression of 5-HT3A and 5-HT3B in these neurons. Our results showed that PNE up-regulated the pulmonary 5-HT concentration and strengthened the PCF 5-HT3R-mediated apnea. PNE significantly facilitated neural excitability by shortening the decay time of 5-HT3R currents, lowering the stimulus threshold, and increasing 5-HT3B IR. In summary, PNE prolongs the apnea mediated by 5-HT3Rs in PCFs, likely by increasing 5-HT3B subunits to enhance the excitability of 5-HT3 channels.-Zhao, L., Gao, X., Zhuang, J., Wallen, M., Leng, S., Xu, F. Prolongation of bronchopulmonary C-fiber-mediated apnea by prenatal nicotinic exposure in rat pups: role of 5-HT3 receptors.

Keywords: TRPV1; cardiovascular activity; sudden infant death syndrome; vagal sensory neurons.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Apnea / etiology*
  • Apnea / genetics
  • Apnea / physiopathology*
  • Biguanides / administration & dosage
  • Bronchoalveolar Lavage Fluid / chemistry
  • Disease Models, Animal
  • Female
  • Humans
  • Infant, Newborn
  • Lung / drug effects*
  • Lung / innervation*
  • Lung / physiopathology
  • Male
  • Nerve Fibers, Unmyelinated / drug effects*
  • Nerve Fibers, Unmyelinated / physiology*
  • Nicotine / administration & dosage
  • Nicotine / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / etiology*
  • Prenatal Exposure Delayed Effects / physiopathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin, 5-HT3 / genetics
  • Receptors, Serotonin, 5-HT3 / physiology*
  • Serotonin / metabolism
  • Serotonin 5-HT3 Receptor Agonists / administration & dosage
  • Sudden Infant Death / etiology


  • Biguanides
  • RNA, Messenger
  • Receptors, Serotonin, 5-HT3
  • Serotonin 5-HT3 Receptor Agonists
  • Serotonin
  • Nicotine
  • phenyl biguanide