ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Chronic nicotine blunts hypoxic sensitivity in perinatal rat adrenal chromaffin cells via upregulation of KATP channels: role of alpha7 nicotinic acetylcholine receptor and hypoxia-inducible factor-2alpha.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- GLP-1 receptor agonists in neurological diseases: mechanisms and therapeutic prospects from metabolism to neuroprotection.Frontiers in immunology · 2026Review
- Gambierol Blocks a KToxins · 2022Article
- Innervated adrenomedullary microphysiological system to model nicotine and opioid exposure.Organs-on-a-chip · 2021Article
- Molecular Mechanisms of Acute Oxygen Sensing by Arterial Chemoreceptor Cells. Role of Hif2α.Frontiers in physiology · 2020Review
- Regulation of catecholamine release from the adrenal medulla is altered in deer mice (American journal of physiology. Regulatory, integrative and comparative physiology · 2019Article
- Distribution of α7 Nicotinic Acetylcholine Receptor Subunit mRNA in the Developing Mouse.Frontiers in neuroanatomy · 2019Article
- Hypoxia-regulated catecholamine secretion in chromaffin cells.Cell and tissue research · 2018Review
- Gene expression analyses reveal metabolic specifications in acute OThe Journal of physiology · 2017Article
- Chronic opioids regulate KATP channel subunit Kir6.2 and carbonic anhydrase I and II expression in rat adrenal chromaffin cells via HIF-2α and protein kinase A.American journal of physiology. Cell physiology · 2014Article
- T-type channel-mediated neurotransmitter release.Pflugers Archiv : European journal of physiology · 2014Review
- Article
- Developmental nicotine exposure alters AMPA neurotransmission in the hypoglossal motor nucleus and pre-Botzinger complex of neonatal rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Chronic exposure of neonatal rat adrenomedullary chromaffin cells to opioids in vitro blunts both hypoxia and hypercapnia chemosensitivity.The Journal of physiology · 2013Article
- Functional chromaffin cell plasticity in response to stress: focus on nicotinic, gap junction, and voltage-gated Ca2+ channels.Journal of molecular neuroscience : MN · 2012Review
- Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2.Physiological reviews · 2012Review
- Developmental and stress-induced remodeling of cell–cell communication in the adrenal medullary tissue.Cellular and molecular neurobiology · 2010Review
- Long-term consequences of fetal and neonatal nicotine exposure: a critical review.Toxicological sciences : an official journal of the Society of Toxicology · 2010Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fetal nicotine exposure blunts hypoxia-induced catecholamine secretion from neonatal adrenomedullary chromaffin cells (AMCs), providing a link between maternal smoking, abnormal arousal responses, and risk of sudden infant death syndrome. Here, we show that the mechanism is attributable to upregulation of K(ATP) channels via stimulation of alpha7 nicotinic ACh receptors (AChRs). These K(ATP) channels open during hypoxia, thereby suppressing membrane excitability. After in utero exposure to chronic nicotine, neonatal AMCs show a blunted hypoxic sensitivity as determined by inhibition of outward K(+) current, membrane depolarization, rise in cytosolic Ca(2+), and catecholamine secretion. However, hypoxic sensitivity could be unmasked in nicotine-exposed AMCs when glibenclamide, a blocker of K(ATP) channels, was present. Both K(ATP) current density and K(ATP) channel subunit (Kir 6.2) expression were significantly enhanced in nicotine-exposed cells relative to controls. The entire sequence could be reproduced in culture by exposing neonatal rat AMCs or immortalized fetal chromaffin (MAH) cells to nicotine for approximately 1 week, and was prevented by coincubation with selective blockers of alpha7 nicotinic AChRs. Additionally, coincubation with inhibitors of protein kinase C and CaM kinase, but not protein kinase A, prevented the effects of chronic nicotine in vitro. Interestingly, chronic nicotine failed to blunt hypoxia-evoked responses in MAH cells bearing short hairpin knockdown (>90%) of the transcription factor, hypoxia-inducible factor-2alpha (HIF-2alpha), suggesting involvement of the HIF pathway. The therapeutic potential of K(ATP) channel blockers was validated in experiments in which hypoxia-induced neonatal mortality in nicotine-exposed pups was significantly reduced after pretreatment with glibenclamide.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.