Macroscopic and macromolecular specificity of alkylphenol anesthetics for neuronal substrates.
Publication/Presentation Date
4-8-2015
Abstract
We used a photoactive general anesthetic called meta-azi-propofol (AziPm) to test the selectivity and specificity of alkylphenol anesthetic binding in mammalian brain. Photolabeling of rat brain sections with [(3)H]AziPm revealed widespread but heterogeneous ligand distribution, with [(3)H]AziPm preferentially binding to synapse-dense areas compared to areas composed largely of cell bodies or myelin. With [(3)H]AziPm and propofol, we determined that alkylphenol general anesthetics bind selectively and specifically to multiple synaptic protein targets. In contrast, the alkylphenol anesthetics do not bind to specific sites on abundant phospholipids or cholesterol, although [(3)H]AziPm shows selectivity for photolabeling phosphatidylethanolamines. Together, our experiments suggest that alkylphenol anesthetic substrates are widespread in number and distribution, similar to those of volatile general anesthetics, and that multi-target mechanisms likely underlie their pharmacology.
Volume
5
First Page
9695
Last Page
9695
ISSN
2045-2322
Published In/Presented At
Weiser, B. P., Hall, M. A., Weinbren, N. L., Woll, K. A., Dailey, W. P., Eckenhoff, M. F., & Eckenhoff, R. G. (2015). Macroscopic and macromolecular specificity of alkylphenol anesthetics for neuronal substrates. Scientific reports, 5, 9695. https://doi.org/10.1038/srep09695
Disciplines
Anesthesiology | Medicine and Health Sciences
PubMedID
25853337
Department(s)
Department of Anesthesiology
Document Type
Article