Prenatal Nicotinic Exposure (PNE) Upregulates Pulmonary 5‐HT and Prolongs Bronchopulmonary C‐fiber (PCF)‐mediated Apnea via Acting on PCF 5‐HT 3 in Rat Pups

Our previous studies have shown a prolonged PCF‐mediated apnea by PNE in rat pups (J. Zhuang et al., Am J Physiol Lung Cell Mol Physiol. 2015), but the relevant mechanisms are not fully elucidated. It is already known that PCFs heavily express 5‐HT 3 and its activation induces apneic response (B. J. Undem et al., J physiol. 2012). Thus, we asked if PNE would upregulate 5‐HT in BALF associated with 5‐HT 3 upregulation in vagal pulmonary C‐neurons and if so, if these changes are involved in the PNE‐induced prolongation of the PCF‐mediated apnea. In P11– 14 rat pups, we compared: 1) 5‐HT content in BALF; 2) 5‐HT 3 protein expression in the nodose ganglion and mRNA level in vagal pulmonary C‐neurons by using single cell RT‐PCR; and 3) the apneic response to right atrial bolus injection of phenylbiguanide (PBG, a selective 5‐HT 3 agonist, 10 μg/kg) in Ctrl and PNE pups. Our results showed that PNE obviously increased 5‐HT in BALF and 5‐HT 3 mRNA level in pulmonary C neurons (retrogradely labeled). Importantly, the apneic duration in response to PBG was significantly longer in PNE than Ctrl pups. We further tested the dependency of the 5‐HT 3 ‐mediated apnea on PCFs and found that the apneic responses to PBG in both Ctrl and PNE pups were blocked by inactivating PCFs with perineural capsaicin treatment (500 μg/ml, 10 min). Our results suggest that PNE is capable of upregulating pulmonary 5‐HT that prolongs the PCF‐mediated apnea via acting on PCF 5‐HT 3 . Support or Funding Information Supported by HL‐107462 and HL‐119683