Year: 2012
Type: article
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. 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.
Source: Journal of Biological Chemistry
Institution: University of Pennsylvania
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W2003904008