title: In vivo activation of azipropofol prolongs anesthesia and reveals synaptic targets.
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.
authors.affiliation: Department of Anesthesia and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Weiser
authors.forename: Max B
authors.initials: MB
authors.lastname: Kelz
authors.forename: Roderic G
authors.initials: RG
authors.lastname: Eckenhoff
mesh_terms: D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D007525:Isoelectric Focusing; D007814:Larva / Q000187:drug effects; D013058:Mass Spectrometry; D015742:Propofol / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects*; D014982:Xenopus laevis / Q000254:growth & development
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol