title: Macroscopic and macromolecular specificity of alkylphenol anesthetics for neuronal substrates.
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.
authors: 1] Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA [2] Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors: Brian P
authors: BP
authors: Weiser
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA.
authors: Michael A
authors: MA
authors: Hall
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA.
authors: Nathan L
authors: NL
authors: Weinbren
authors: 1] Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA [2] Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors: Kellie A
authors: KA
authors: Woll
authors: Department of Chemistry, University of Pennsylvania, Philadelphia, PA.
authors: William P
authors: WP
authors: Dailey
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA.
authors: Maryellen F
authors: MF
authors: Eckenhoff
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA.
authors: Roderic G
authors: RG
authors: Eckenhoff
mesh_terms: D000777:Anesthetics / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D015742:Propofol / Q000493:pharmacokinetics / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats
chemical_list: D000777:Anesthetics; D008055:Lipids; D015742:Propofol