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-HT ₃ R 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.