In vivo activation of azipropofol prolongs anesthesia and reveals synaptic targets

Brian P. Weiser, Max B. Kelz, Roderic G. Eckenhoff

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1279-1285
Number of pages7
JournalJournal of Biological Chemistry
Volume288
Issue number2
DOIs
StatePublished - Jan 11 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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