ArticleMolecular pharmacology2015
Mutational Analysis of the Putative High-Affinity Propofol Binding Site in Human β3 Homomeric GABAA Receptors.
Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Activation of the human β3 GABABiochemical pharmacology · 2026Article
- Properties of Acute Activation and Inhibition of the β3 Homomeric GABAACS chemical neuroscience · 2025Article
- Null method to estimate the maximal PA at subsaturating concentrations of agonist.The Journal of general physiology · 2025Article
- Phenols and GABAFrontiers in pharmacology · 2024Review
- Dendritic spine remodeling and plasticity under general anesthesia.Brain structure & function · 2021Review
- GABAJournal, genetic engineering & biotechnology · 2021Review
- Steady-state activation and modulation of the synaptic-type α1β2γ2L GABAPhysiological reports · 2019Article
- Multiple functional neurosteroid binding sites on GABAA receptors.PLoS biology · 2019Article
- Analysis of GABAMolecular pharmacology · 2019Article
- Structural basis of neurosteroid anesthetic action on GABANature communications · 2018Article
- Comparison of αβδ and αβγ GABAPharmacological research · 2018Review
- High Constitutive Activity Accounts for the Combination of Enhanced Direct Activation and Reduced Potentiation in Mutated GABAMolecular pharmacology · 2018Article
- Propofol Is an Allosteric Agonist with Multiple Binding Sites on Concatemeric Ternary GABAMolecular pharmacology · 2018Article
- Recent progress on the molecular pharmacology of propofol.F1000Research · 2018Review
- Tryptophan and Cysteine Mutations in M1 Helices of α1β3γ2L γ-Aminobutyric Acid Type A Receptors Indicate Distinct Intersubunit Sites for Four Intravenous Anesthetics and One Orphan Site.Anesthesiology · 2016Article
- Mapping General Anesthetic Sites in Heteromeric γ-Aminobutyric Acid Type A Receptors Reveals a Potential For Targeting Receptor Subtypes.Anesthesia and analgesia · 2016Review
- A Novel Bifunctional Alkylphenol Anesthetic Allows Characterization of γ-Aminobutyric Acid, Type A (GABAA), Receptor Subunit Binding Selectivity in Synaptosomes.The Journal of biological chemistry · 2016Article
- Multiple Non-Equivalent Interfaces Mediate Direct Activation of GABAA Receptors by Propofol.Current neuropharmacology · 2016Review
- A Cysteine Substitution Probes β3H267 Interactions with Propofol and Other Potent Anesthetics in α1β3γ2L γ-Aminobutyric Acid Type A Receptors.Anesthesiology · 2016Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Propofol is a sedative and anesthetic agent that can both activate GABA(A) receptors and potentiate receptor activation elicited by submaximal concentrations of the transmitter. A recent modeling study of the β3 homomeric GABA(A) receptor postulated a high-affinity propofol binding site in a hydrophobic pocket in the middle of a triangular cleft lined by the M1 and M2 membrane-spanning domains of one subunit and the M2 domain of the neighboring subunit. The goal of the present study was to gain functional evidence for the involvement of this pocket in the actions of propofol. Human β3 and α1β3 receptors were expressed in Xenopus oocytes, and the effects of substitutions of selected residues were probed on channel activation by propofol and pentobarbital. The data demonstrate the vital role of the β3(Y143), β3(F221), β3(Q224), and β3(T266) residues in the actions of propofol but not pentobarbital in β3 receptors. The effects of β3(Y143W) and β3(Q224W) on activation by propofol are likely steric because propofol analogs with less bulky ortho substituents activated both wild-type and mutant receptors. The T266W mutation removed activation by propofol in β3 homomeric receptors; however, this mutation alone or in combination with a homologous mutation (I271W) in the α1 subunit had almost no effect on activation properties in α1β3 heteromeric receptors. We hypothesize that heteromeric α1β3 receptors can be activated by propofol interactions with β3-β3, α1-β3, and β3-α1 interfaces, but the exact locations of the binding site and/or nature of interactions vary in different classes of interfaces.
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