Prolongation of bronchopulmonary C‐fiber–mediated apnea by prenatal nicotinic exposure in rat pups: role of 5‐HT₃receptors

Abstract

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. FASEB J. 33, 10731–10741 (2019). http://www.fasebj.org

Cross-effect of TRPV1 and EP3 receptor on coughs and bronchopulmonary C-neural activities

“…The nodose/jugular ganglia of guinea pigs (n = 15) pretreated with DiI were extracted, primary neurons were cultured overnight, and the currents triggered by PGE 2 - or CAP were recorded on neurons labeled with DiI and a cell size less than 20 μm by using the whole-cell patch clamp technique. PGE 2 or CAP was ejected onto the target neuron via a pipette (~15 μm away) driven by air pressure in the following six sets of the experiment: 1) and 2) the currents induced by CAP (1.5 μM) [ 38 , 41 ] and PGE 2 (up to 20 μM) [ 42 ] were recorded respectively; 3) and 4) CAP-induced currents were recorded with application of JNJ 17203212 (20 μM) or L-798106 (6 μM) [ 40 , 43 ] in the bath solution 30 min prior to CAP; and 5) and 6) the same protocols mentioned in 3) and 4) were carried out with the exception that PGE 2 -, but not CAP-, currents were recorded.…”

Interaction of TRPV1 and EP3 Receptor in Cough and Bronchopulmonary C-Neural Activities

“…The nodose/jugular ganglia of guinea pigs (n = 15) pretreated with DiI were extracted, primary neurons were cultured overnight, and the currents triggered by PGE 2 -or CAP were recorded on neurons labeled with DiI and a cell size less than 20 µm by using the whole-cell patch clamp technique. PGE 2 or CAP was ejected onto the target neuron via a pipette (~ 15 µm away) driven by air pressure in the following six sets of the experiment: 1) and 2) the currents induced by CAP (1.5 µM) [36,39] and PGE 2 (up to 20 µM) [40] were recorded respectively; 3) and 4) CAP-induced currents were recorded with application of JNJ 17203212 (20 µM) or L-798106 (6 µM) [38,41] in the bath solution 30 min prior to CAP; and 5) and 6) the same protocols mentioned in 3) and 4) were carried out with the exception that PGE 2 -, but not CAP-, currents were recorded.…”