ArticleAnesthesiology2008
Photo-activated azi-etomidate, a general anesthetic photolabel, irreversibly enhances gating and desensitization of gamma-aminobutyric acid type A receptors.
Article in Anesthesiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- The Modulation by Anesthetics and Analgesics of Respiratory Rhythm in the Nervous System.Current neuropharmacology · 2024Review
- GABAFrontiers in aging neuroscience · 2021Article
- Comparison of αβδ and αβγ GABAPharmacological research · 2018Review
- Non-blocking modulation contributes to sodium channel inhibition by a covalently attached photoreactive riluzole analog.Scientific reports · 2018Article
- Optoanesthesia: Use of Anesthetic Photolabels In Vivo.Methods in enzymology · 2018Article
- Shedding Light on Anesthetic Mechanisms: Application of Photoaffinity Ligands.Anesthesia and analgesia · 2016Review
- Inter- and Intra-Subunit Butanol/Isoflurane Sites of Action in the Human Glycine Receptor.Frontiers in molecular neuroscience · 2016Article
- Etomidate uniquely modulates the desensitization of recombinant α1β3δ GABA(A) receptors.Neuroscience · 2015Article
- Photo-antagonism of the GABAA receptor.Nature communications · 2014Article
- Mechanisms revealed through general anesthetic photolabeling.Current anesthesiology reports · 2014Article
- State-dependent etomidate occupancy of its allosteric agonist sites measured in a cysteine-substituted GABAA receptor.Molecular pharmacology · 2013Article
- In vivo activation of azipropofol prolongs anesthesia and reveals synaptic targets.The Journal of biological chemistry · 2013Article
- Allosteric nature of P2X receptor activation probed by photoaffinity labelling.British journal of pharmacology · 2012Article
- An allosteric coagonist model for propofol effects on α1β2γ2L γ-aminobutyric acid type A receptors.Anesthesiology · 2012Article
- Mutations in the GABAA receptor that mimic the allosteric ligand etomidate.Methods in molecular biology (Clifton, N.J.) · 2012Article
- Clinical and molecular pharmacology of etomidate.Anesthesiology · 2011Review
- Gamma-amino butyric acid type A receptor mutations at beta2N265 alter etomidate efficacy while preserving basal and agonist-dependent activity.Anesthesiology · 2009Article
- Tryptophan mutations at azi-etomidate photo-incorporation sites on alpha1 or beta2 subunits enhance GABAA receptor gating and reduce etomidate modulation.Molecular pharmacology · 2008Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe general anesthetic etomidate acts via gamma-aminobutyric acid type A (GABA(A)) receptors, enhancing activation at low GABA and prolonging deactivation. Azi-etomidate is a photo-reactive etomidate derivative with similar pharmacological actions, which has been used to identify putative binding sites. The authors examine the irreversible effects of azi-etomidate photo-modification on functional GABA(A) receptors in cell membranes.
methodsGABA(A) receptors (alpha1beta2gamma2L) were expressed in both Xenopus oocytes and human embryonic kidney cells exposed to 365 nm light-activated azi-etomidate with or without GABA, then extensively washed. Receptor-mediated chloride currents were measured using voltage clamp electrophysiology to assess the ratio of peak responses at 10 microm and 1 mm GABA (I10/I1000) and deactivation time course.
resultsAfter azi-etomidate photo-modification, I10/I1000 ratios were persistently enhanced and deactivation was prolonged, mimicking reversible azi-etomidate actions. Azi-etomidate and ultraviolet light were required to produce irreversible receptor modulation. Adding GABA during photo-modification greatly enhanced irreversible modulation. Azi-etomidate modification also dose-dependently reduced maximal GABA-activated currents, consistent with accumulation of permanently desensitized receptors. Excess etomidate during azi-etomidate photo-modification competitively reduced permanent desensitization. Persistent channel modulation was blocked by 320-fold excess etomidate but enhanced when 32-fold excess etomidate was present.
conclusionsAzi-etomidate efficiently photo-modifies etomidate sites on GABA(A) receptors in intact cells, producing persistent functional changes that mimic its reversible effects. The results demonstrate sequential modification at more than one etomidate site per receptor. The sites display reciprocal positive cooperativity. In combination with focal photo-activation, azi-etomidate may prove useful for studies of anesthetic actions in neural circuits.
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