ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2001
The C terminus of the human nicotinic alpha4beta2 receptor forms a binding site required for potentiation by an estrogenic steroid.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
56 citing papers in PubMed, 143 citations in OpenAlex.
- The relationship between apparent potentiation and the magnitude of the control response.The Journal of general physiology · 2026Article
- Contraceptive hormone ethinyl estradiol but not levonorgestrel modulates the role of reinforcer-enhancement in nicotine self-administration in ovary-intact female Sprague-Dawley rats.Neuropharmacology · 2025Article
- Unravelling the multifaceted actions of neurosteroids: Machine learning and in vitro screening for novel target discovery.British journal of pharmacology · 2025Article
- Systemically circulating 17β-estradiol enhances the neuroprotective effect of the smoking cessation drug cytisine in female parkinsonian mice.NPJ Parkinson's disease · 2025Article
- Nicotine is an Immunosuppressant: Implications for Women's Health and Disease.Journal of neuroimmunology · 2024Review
- Divergent mechanisms of steroid inhibition in the human ρ1 GABANature communications · 2024Article
- Adolescent nicotine exposure induces long-term, sex-specific disturbances in mood and anxiety-related behavioral, neuronal and molecular phenotypes in the mesocorticolimbic system.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Neurosteroid enantiomers as potentially novel neurotherapeutics.Neuroscience and biobehavioral reviews · 2023Review
- The importance of translationally evaluating steroid hormone contributions to substance use.Frontiers in neuroendocrinology · 2023Review
- Developmental nicotine exposure and masculinization of the rat preoptic area.Neurotoxicology · 2022Article
- Discovery and functional characterization of N-(thiazol-2-yl)-benzamide analogs as the first class of selective antagonists of the Zinc-Activated Channel (ZAC).Biochemical pharmacology · 2021Article
- E-cigarette vape and lung ACE2 expression: Implications for coronavirus vulnerability.Environmental toxicology and pharmacology · 2021Article
- The functional role of the αM4 transmembrane helix in the muscle nicotinic acetylcholine receptor probed through mutagenesis and coevolutionary analyses.The Journal of biological chemistry · 2020Article
- The molecular nature of the 17β-Estradiol binding site in the voltage- and CaScientific reports · 2019Article
- Sex differences in stress reactivity in arousal and attention systems.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Review
- Nicotinic acetylcholine receptors at the single-channel level.British journal of pharmacology · 2018Review
- Orthosteric and allosteric potentiation of heteromeric neuronal nicotinic acetylcholine receptors.British journal of pharmacology · 2018Review
- Mapping two neurosteroid-modulatory sites in the prototypic pentameric ligand-gated ion channel GLIC.The Journal of biological chemistry · 2018Article
- Current Perspectives for the use of Gonane Progesteronergic Drugs in the Treatment of Central Hypoventilation Syndromes.Current neuropharmacology · 2018Review
- α2* Nicotinic acetylcholine receptors influence hippocampus-dependent learning and memory in adolescent mice.Learning & memory (Cold Spring Harbor, N.Y.) · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In addition to actions mediated by changes in gene expression, steroids can directly modulate several transmitter-gated and voltage-gated ion channels. Despite numerous studies showing that steroids enhance or reduce ion channel activity, the site(s) that mediates steroid recognition is not known. To identify the regions in which steroids bind and affect ion channel activity, we have taken advantage of the observation that human alpha4beta2 neuronal nicotinic receptors are potentiated by an estrogen steroid, 17beta-estradiol, whereas a rat alpha4beta2 receptor is not. Mutations indicate that a sequence (AGMI) at the end of the C terminus of the human alpha4 subunit forms a binding site required for 17beta-estradiol potentiation. In contrast, ethynyl beta-estradiol (an oral contraceptive) potentiates both human and rat alpha4beta2 receptors. A single tryptophan in the C terminus of both the rat and the human alpha4 subunit is sufficient for potentiation by ethynyl beta-estradiol, probably through a pi-pi interaction. Mutation of this tryptophan eliminates the ability of ethynyl beta-estradiol to potentiate rat receptors. However, in human receptors it was necessary to mutate both the AGMI sequence and the tryptophan to eliminate potentiation by ethynyl beta-estradiol. The findings that beta-estradiol requires the AGMI sequence but that a single C-terminal tryptophan is sufficient for potentiation by ethynyl beta-estradiol indicate that the C terminus forms a binding site for these steroids. The binding site(s) for block appears to differ from those involved in potentiation because the C-terminal sequence does not affect block by steroids such as progesterone, and progesterone does not competitively inhibit potentiation.
Indexed as
Identifiers
11517245PMC6763114W2112897543What OpenQuestion holds
Registered trials
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.