ArticleAnesthesiology2012
Two etomidate sites in α1β2γ2 γ-aminobutyric acid type A receptors contribute equally and noncooperatively to modulation of channel gating.
Article in Anesthesiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed.
- Alchemical Free Energy Perturbation Predicts Relative Binding Affinities of Propofol Analogs and Etomidate Stereoisomers at the GABAACS omega · 2026Article
- Article
- Structural insights into GABANature communications · 2024Article
- Correlations of receptor desensitization of gain-of-function GABRB3 variants with clinical severity.Brain : a journal of neurology · 2024Article
- Mutational Analysis of Anesthetic Binding Sites and Their Effects on GABABiomolecules · 2023Article
- Isoflurane inhibition of endocytosis is an anesthetic mechanism of action.Current biology : CB · 2022Article
- Intrasubunit and Intersubunit Steroid Binding Sites Independently and Additively MediateMolecular pharmacology · 2021Article
- Surgical Site Infections and Perioperative Optimization of Host Immunity by Selection of Anesthetics.BioMed research international · 2021Review
- Steady-State Activation and Modulation of the ConcatemericMolecular pharmacology · 2019Article
- Monod-Wyman-Changeux Allosteric Shift Analysis in MutantMolecular pharmacology · 2019Article
- Etomidate and Etomidate Analog Binding and Positive Modulation of γ-Aminobutyric Acid Type A Receptors: Evidence for a State-dependent Cutoff Effect.Anesthesiology · 2018Article
- Comparison of αβδ and αβγ GABAPharmacological research · 2018Review
- Competitive Antagonism of Anesthetic Action at the γ-Aminobutyric Acid Type A Receptor by a Novel Etomidate Analog with Low Intrinsic Efficacy.Anesthesiology · 2017Article
- Novel positive allosteric modulators of GABAA receptors with anesthetic activity.Scientific reports · 2016Article
- γ-Aminobutyric Acid Type A Receptor Modulation by Etomidate Analogs.Anesthesiology · 2016Article
- Article
- Positive and Negative Allosteric Modulation of an α1β3γ2 γ-Aminobutyric Acid Type A (GABAA) Receptor by Binding to a Site in the Transmembrane Domain at the γ+-β- Interface.The Journal of biological chemistry · 2015Article
- Etomidate produces similar allosteric modulation in α1β3δ and α1β3γ2L GABA(A) receptors.British journal of pharmacology · 2014Article
- Mutations at beta N265 in γ-aminobutyric acid type A receptors alter both binding affinity and efficacy of potent anesthetics.PloS one · 2014Article
- Cysteine substitutions define etomidate binding and gating linkages in the α-M1 domain of γ-aminobutyric acid type A (GABAA) receptors.The Journal of biological chemistry · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
backgroundEtomidate is a potent hypnotic agent that acts via γ-aminobutyric acid receptor type A (GABA(A)) receptors. Evidence supports the presence of two etomidate sites per GABA(A) receptor, and current models assume that each site contributes equally and noncooperatively to drug effects. These assumptions remain untested.
methodsWe used concatenated dimer (β2-α1) and trimer (γ2-β2-α1) GABA(A) subunit assemblies that form functional α1β2γ2 channels, and inserted α1M236W etomidate site mutations into both dimers (β2-α1M236W) and trimers (γ2-β2-α1M236W). Wild-type or mutant dimers (D(wt) or D(αM236W)) and trimers (T(wt) or T(αM236W)) were coexpressed in Xenopus oocytes to produce four types of channels: D(wt)T(wt), D(αM236W)T(wt), D(wt)T(αM236W), and D(αM236W)T(αM236W). For each channel type, two-electrode voltage clamp was performed to quantitatively assess GABA EC(50), etomidate modulation (left shift), etomidate direct activation, and other functional parameters affected by αM236W mutations.
resultsConcatenated wild-type D(wt)T(wt) channels displayed etomidate modulation and direct activation similar to α1β2γ2 receptors formed with free subunits. D(αM236W)T(αM236W) receptors also displayed altered GABA sensitivity and etomidate modulation similar to mutated channels formed with free subunits. Both single-site mutant receptors (D(αM236W)T(wt) and D(wt)T(αM236W)) displayed indistinguishable functional properties and equal gating energy changes for GABA activation (-4.9 ± 0.48 vs. -4.7 ± 0.48 kJ/mol, respectively) and etomidate modulation (-3.4 ± 0.49 vs. -3.7 ± 0.38 kJ/mol, respectively), which together accounted for the differences between D(wt)T(wt) and D(αM236W)T(αM236W) channels.
conclusionsThese results support the hypothesis that the two etomidate sites on α1β2γ2 GABA(A) receptors contribute equally and noncooperatively to drug interactions and gating effects.
Indexed as
Identifiers
What 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.