In vivo activation of azipropofol prolongs anesthesia and reveals synaptic targets
Open accessAbstract
General anesthetic photolabels have been instrumental in discovering and confirming protein binding partners and binding sites of these promiscuous ligands. We report the in vivo photoactivation of meta -azipropofol, a potent analog of propofol, in Xenopus laevis tadpoles. Covalent adduction of meta -azipropofol in vivo prolongs the primary pharmacologic effect of general anesthetics in a behavioral phenotype we termed "optoanesthesia." Coupling this behavior with a tritiated probe, we performed unbiased, time-resolved gel proteomics to identify neuronal targets of meta -azipropofol in vivo . We have identified synaptic binding partners, such as synaptosomal-associated protein 25, as well as voltage-dependent anion channels as potential facilitators of the general anesthetic state. Pairing behavioral phenotypes elicited by the activation of efficacious photolabels in vivo with time-resolved proteomics provides a novel approach to investigate molecular mechanisms of general anesthetics. Background: Azipropofol is a photoactive analog of the general anesthetic propofol. Results: In vivo photolabeling of tadpoles results in covalent ligand binding to neuronal proteins and prolongation of anesthesia. Conclusion: Reconciling time-resolved gel proteomics with behavioral state allows identification of potential anesthetic targets. Significance: In vivo activation of efficacious photolabels provides a novel approach to investigate mechanisms of general anesthesia.
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Volatile anesthetics bind directly to syntaxin and the SNARE complex.
“Volatile anesthetics have been shown to bind directly to syntaxin and the SNARE complex [76, 77].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [77]
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Self-citation
- Authors
- Weiser, B. P., Kelz, M. B., & Eckenhoff, R. G.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Eckenhoff, Roderic G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 288
- Issue
- 2
- Pages
- 1279-1285
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3543011
- OpenAlex
- W2003904008
- Cited by
- 29
- References
- 39
- Citations by year
- 2026: 1 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 7 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 3
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health (GM055876)
- National Institute of General Medical Sciences (GM055876, GM088156, R01GM088156, P01GM055876)
- National Institute of Neurological Disorders and Stroke (NS080519, F31NS080519)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- general anesthetics, SNAP-25, voltage-dependent anion channel, Xenopus laevis tadpoles
- MeSH terms
- Animals, Electrophoresis, Polyacrylamide Gel, Isoelectric Focusing, Larva, Mass Spectrometry, Synapses, Xenopus laevis, Propofol, Anesthetics, Intravenous
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