In Vivo Activation of Azipropofol Prolongs Anesthesia and Reveals Synaptic Targets |
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Authors: | Brian P Weiser Max B Kelz Roderic G Eckenhoff |
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Institution: | From the ‡Department of Anesthesia and Critical Care.;§Department of Pharmacology.;¶Center for Sleep and Circadian Neurobiology, and ;‖Mahoney Institute of Neurological Sciences, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104 |
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Abstract: | 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. |
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Keywords: | Anesthesia Neurobiology Photoaffinity Labeling Protein Chemical Modification Xenopus Xenopus laevis Azipropofol Propofol Tadpole |
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