ArticleBritish journal of pharmacology2013
A study of subunit selectivity, mechanism and site of action of the delta selective compound 2 (DS2) at human recombinant and rodent native GABA(A) receptors.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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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.
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.
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Who cites it
50 citing papers in PubMed, 81 citations in OpenAlex.
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- Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery.Frontiers in cellular neuroscience · 2022Review
- Tonic GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Structural determinants and regulation of spontaneous activity in GABANature communications · 2021Article
- The efficacy of γ-aminobutyric acid type A receptor (GABAToxicology and applied pharmacology · 2021Article
- GABAJournal, genetic engineering & biotechnology · 2021Review
- Pharmacological and Biophysical Characteristics of Picrotoxin-Resistant, δSubunit-Containing GABAFrontiers in synaptic neuroscience · 2021Article
- Allosteric Modulation of GABAACS pharmacology & translational science · 2020Article
- Silencing of spontaneous activity at α4β1/3δ GABABritish journal of pharmacology · 2020Article
- Realising the therapeutic potential of neuroactive steroid modulators of the GABANeurobiology of stress · 2020Article
- Allosteric GABAMolecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
background and purposeMost GABA(A) receptor subtypes comprise 2α, 2β and 1γ subunit, although for some isoforms, a δ replaces a γ-subunit. Extrasynaptic δ-GABA(A) receptors are important therapeutic targets, but there are few suitable pharmacological tools. We profiled DS2, the purported positive allosteric modulator (PAM) of δ-GABA(A) receptors to better understand subtype selectivity, mechanism/site of action and activity at native δ-GABA(A) receptors. EXPERIMENTAL APPROACH: Subunit specificity of DS2 was determined using electrophysiological recordings of Xenopus laevis oocytes expressing human recombinant GABA(A) receptor isoforms. Effects of DS2 on GABA concentration-response curves were assessed to define mechanisms of action. Radioligand binding and electrophysiology utilising mutant receptors and pharmacology were used to define site of action. Using brain-slice electrophysiology, we assessed the influence of DS2 on thalamic inhibition in wild-type and δ(0/0) mice. KEY
resultsActions of DS2 were primarily determined by the δ-subunit but were additionally influenced by the α, but not the β, subunit (α4/6βxδ > α1βxδ >> γ2-GABA(A) receptors > α4β3). For δ-GABA(A) receptors, DS2 enhanced maximum responses to GABA, with minimal influence on GABA potency. (iii) DS2 did not act via the orthosteric, or known modulatory sites on GABA(A) receptors. (iv) DS2 enhanced tonic currents of thalamocortical neurones from wild-type but not δ(0/0) mice. CONCLUSIONS AND IMPLICATIONS: DS2 is the first PAM selective for α4/6βxδ receptors, providing a novel tool to investigate extrasynaptic δ-GABA(A) receptors. The effects of DS2 are mediated by an unknown site leading to GABA(A) receptor isoform selectivity.
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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.