Recruitment of GABA(A) receptors in chemoreceptor pulmonary neuroepithelial bodies by prenatal nicotine exposure in monkey lung.
Pulmonary neuroepithelial bodies (NEB) act as airway oxygen sensors and produce serotonin, a variety of neuropeptides and are involved in autonomic nervous system control of breathing, especially during the neonatal period. We now report that NEB cells also express a GABAergic signaling loop that is increased by prenatal nicotine exposure. In this study, cultured monkey NEB cells show hypoxia-evoked action potentials and hypoxia-sensitive K(+) current. As shown by both immunofluorescence and RT-PCR, monkey NEB cells synthesize and contain serotonin. The monkey NEB cells express the beta2 and beta3 GABA_A receptor subunits, GAD and also express alpha7, alpha4 and beta4 nicotinic receptor (nAChR) subunits. The alpha7 nAChR is co-expressed with GAD in NEB. The numbers of NEB and beta3 GABA_A receptor subunits expressed in NEB cells in lungs from control newborn monkeys were compared to lungs from animals that received nicotine during gestation. Prenatal nicotine exposure increased the numbers of NEB by 46% in lung and the numbers of NEB cells expressing GAD and GABA_A beta3 receptors increased by 67% and 66%, respectively. This study suggests that prenatal nicotine exposure can modulate NEB function by increasing the numbers of NEB cells and by increasing both GAD expression and beta3 GABA_A receptor subunit expression. The interaction of the intrinsic GABAergic system in the lung with nicotinic receptors in PNEC/NEB may provide a mechanism to explain the link between smoking during pregnancy and SIDS.
Fu
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Division of Neuroscience, Oregon National Primate Research Center, Health & Science University, Oregon, Beaverton, OR, USA. fuxiao@ohsu.edu
Spindel
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D004553:Electric Conductivity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D000860:Hypoxia / Q000378:metabolism; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D008253:Macaca mulatta; D018811:Maternal Exposure; D046568:Neuroepithelial Bodies / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D011963:Receptors, GABA-A; D009538:Nicotine; D011188:Potassium