Prolongation of bronchopulmonary C‐fiber–mediated apnea by prenatal nicotinic exposure in rat pups: role of 5‐HT 3 receptors

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‐HT 3 R) in PCFs, and among the 5‐HT3R subunits, 5‐HT 3B is responsible for shortening the decay time of 5‐HT 3 R—mediated currents. We examined whether PNE would promote pulmonary 5‐HT secretion and prolong the apnea mediated by 5‐HT 3 Rs in PCFs via affecting the 5‐HT 3B 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‐HT 3 R agonist) before and after PCF inactivation, 3 ) 5‐HT 3 R currents and the stimulus threshold of the action currents of vagal pulmonary C‐neurons, and 4 ) the immunoreactivity (IR) and mRNA expression of 5‐HT 3A and 5‐HT 3B in these neurons. Our results showed that PNE up‐regulated the pulmonary 5‐HT concentration and strengthened the PCF 5‐HT 3 R‐mediated apnea. PNE significantly facilitated neural excitability by shortening the decay time of 5‐HT 3 R currents, lowering the stimulus threshold, and increasing 5‐HT 3B IR. In summary, PNE prolongs the apnea mediated by 5‐HT 3 Rs in PCFs, likely by increasing 5‐HT 3B subunits to enhance the excitability of 5‐HT 3 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‐HT 3 receptors. FASEB J. 33, 10731–10741 (2019). www.fasebj.org