title: Inhaled anesthetics elicit region-specific changes in protein expression in mammalian brain.
abstract: Inhaled anesthetics bind specifically to many proteins in the mammalian brain. Within the subgroup of proteins whose activity is substantially modulated by anesthetic binding, it is reasonable to expect anesthetic-induced alterations in host expression level. Thus, in an attempt to define the group of functional targets for these commonly used drugs, we examined changes in protein expression after anesthetic exposure in both intact rodent brains and in neuronal cell culture. Differential in-gel electrophoresis was used to minimize variance, in order to detect small changes. Quantitative analysis shows that 5 h exposures to 1 minimum alveolar concentration (1 MAC) halothane caused changes in the expression of approximately 2% of detectable proteins, but only at 2-24 h after awakening, and only in the cortex. An equipotent concentration of isoflurane altered the expression of only approximately 1% of detectable proteins, and only in the hippocampus. Primary cortical neurons were exposed to three-fold higher concentrations of anesthetics with no evidence of cytotoxicity. Small changes in protein expression were elicited by both drugs. Despite the fact that anesthetics produce profound changes in neurobiology and behavior, we found only minor changes in brain protein expression. A pronounced degree of regional selectivity was noted, indicating an under appreciated degree of specificity for these promiscuous drugs.
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. roderic.eckenhoff@uphs.upenn.edu
authors.forename: Jonathan Z
authors.initials: JZ
authors.lastname: Pan
authors.forename: Jin
authors.initials: J
authors.lastname: Xi
authors.forename: Maryellen F
authors.initials: MF
authors.lastname: Eckenhoff
authors.forename: Roderic G
authors.initials: RG
authors.lastname: Eckenhoff
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D006221:Halothane / Q000008:administration & dosage*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007261:Infusions, Intra-Arterial; D007530:Isoflurane / Q000008:administration & dosage*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane; D006221:Halothane