Premium
Prenatal Nicotinic Exposure Prolongs the Apneic Response to Activation of Bronchopulmonary C‐fiber 5‐HT3 Receptor with Upregulation of C‐neural 5‐HT3B Expression in Rat Pups
Author(s) -
Zhao Lei,
Gao Xiuping,
Zhuang Jianguo,
Shi Yuanyuan,
Xu Fadi
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.625.12
Subject(s) - homomeric , receptor , nicotinic agonist , 5 ht3 receptor , trpv1 , medicine , patch clamp , endocrinology , chemistry , agonist , capsaicin , downregulation and upregulation , stimulation , desensitization (medicine) , serotonin , 5 ht receptor , biology , protein subunit , transient receptor potential channel , biochemistry , gene
5‐HT3 receptor, an important ionic channel, is heavily expressed in bronchopulmonary C‐fibers (PCFs). Among five 5‐HT3 receptor subunits (5‐HT3A–E), only homomeric 5‐HT3A and heteromeric 5‐HT3AB form functional ion channels. It is reported that the recovery from channel desensitization is much faster in 5‐HT3AB receptor assemblies than that in 5‐HT3A receptor assemblies. Our previous studies have shown that prenatal nicotinic exposure (PNE) significantly prolongs the apneic response to stimulation of PCFs in rat pups. Here, we asked whether PNE would promote 5‐HT secretion in BALF and prolong the 5‐HT3‐mediated apneic response depending on PCFs. We further asked whether this augmented 5‐HT3‐mediated response was associated with alterations of protein and mRNA expressions of 5‐HT3A and/or 5‐HT3B subunits and changes of 5‐HT3 currents in vagal pulmonary C‐neurons. To this end, Ctrl and PNE rat pups were used to detect the differences in: 1) 5‐HT content in BALF; 2) the apneic response to right atrial bolus injection of phenylbiguanide (a selective 5‐HT3 agonist, 10 μg/kg) under PCF intact condition and degenerated condition induced by perivagal capsaicin treatment; 3) 5‐HT3A and 5‐HT3B mRNA (single cell RT‐PCR) and protein expression (immunohistochemistry) in the nodose/jugular ganglionic vagal pulmonary C‐neurons that were retrogradely traced by intratracheal instillation of DiI and marked with TRPV1 expression; and 4) 5‐HT3 currents on these neurons recorded by patch‐clamp in vitro. Our results show that PNE not only upregulates pulmonary 5‐HT concentration but also strengthens the 5‐HT3‐mediated apnea depending on PCF. PNE increases 5‐HT3B but not 5‐HT3A protein expression with little changes in their mRNA level in the vagal pulmonary C‐neurons. Interestingly, PNE significantly accelerates 5‐HT3 channel desensitization and shortens the half‐widths and decay times but has no effect on the rise‐times of these channels. Our results suggest that PNE prolongs PCF 5‐HT3‐mediated apnea likely through altering the formation of 5‐HT subunits (increasing 5‐HT3B) to enhance the sensitivities of 5‐HT3 channels. Support or Funding Information HL119683 and HL107462 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .