Sites of volatile anesthetic action on kainate (Glutamate receptor 6) receptors.

The Journal of Biological Chemistry
K MinamiR A Harris

Abstract

Molecular mechanisms of anesthetic action on neurotransmitter receptors are poorly understood. The major excitatory neurotransmitter in the central nervous system is glutamate, and recent studies found that volatile anesthetics inhibit the function of the alpha-amino-3-hydroxyisoxazolepropionic acid subtype of glutamate receptors (e.g. glutamate receptor 3 (GluR3)), but enhance kainate (GluR6) receptor function. We used this dissimilar pharmacology to identify sites of anesthetic action on the kainate GluR6 receptor by constructing chimeric GluR3/GluR6 receptors. Results with chimeric receptors implicated a transmembrane region (TM4) of GluR6 in the action of halothane. Site-directed mutagenesis subsequently showed that a specific amino acid, glycine 819 in TM4, is important for enhancement of receptor function by halothane (0. 2-2 mM). Mutations of Gly-819 also markedly decreased the response to isoflurane (0.2-2 mM), enflurane (0.2-2 mM), and 1-chloro-1,2, 2-trifluorocyclobutane (0.2-2 mM). The nonanesthetics 1, 2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane had no effect on the functions of either wild-type GluR6 or receptors mutated at Gly-819. Ethanol and pentobarbital inhibited the function of both wild-...Continue Reading

References

Dec 1, 1992·Anesthesiology·C McFarlaneL Nordholm
Jul 1, 1992·Trends in Pharmacological Sciences·B Sommer, P H Seeburg
Dec 1, 1991·Pharmacology, Biochemistry, and Behavior·L C Daniell
Feb 1, 1986·British Journal of Pharmacology·S G Agrawal, R H Evans
Nov 1, 1968·Journal of Theoretical Biology·J M ZimmermanR Simha
Jun 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·T P Hopp, K R Woods
May 5, 1982·Journal of Molecular Biology·J Kyte, R F Doolittle
Feb 17, 1994·Nature·N P Franks, W R Lieb
Apr 1, 1995·Trends in Neurosciences·Z G Wo, R E Oswald
Dec 1, 1994·Anesthesia and Analgesia·D D KoblinP Ionescu
Jan 1, 1994·Annual Review of Neuroscience·M Hollmann, S Heinemann
May 1, 1996·British Journal of Pharmacology·J E Dildy-MayfieldR A Harris
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·D C RubinszteinD Craufurd
Jul 10, 1997·Nature·M Vignes, G L Collingridge

❮ Previous
Next ❯

Citations

Sep 16, 1999·Cellular and Molecular Life Sciences : CMLS·M D Krasowski, N L Harrison
Dec 25, 2010·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Dian-Shi Wang, Beverley A Orser
Sep 21, 2000·Journal of Neuroscience Methods·A RozzaL Montalbetti
Jan 1, 1999·Trends in Pharmacological Sciences·L J ChandlerF T Crews
Aug 28, 1999·Progress in Neurobiology·T Yamakura, K Shimoji
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·S KaechA Matus
Nov 4, 2010·The Journal of Biological Chemistry·Amanda M StyerTooraj Mirshahi
Jun 11, 2009·British Journal of Anaesthesia·H C Hemmings
Apr 20, 2002·Anesthesiology·Robert DickinsonNicholas P Franks
Apr 20, 2002·Anesthesiology·Joseph F AntogniniRichard Atherley
Jul 20, 2002·Anesthesiology·Pamela FloodKristen M Coates
Jan 24, 2004·Anesthesiology·Andrew J R PlestedNicholas P Franks
Jun 6, 2009·European Journal of Anaesthesiology·Andrea Kopp LugliChristoph H Kindler
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·T YamakuraR A Harris
Aug 21, 2008·Anesthesia and Analgesia·Edmond I EgerJames M Sonner
Feb 10, 2006·Epilepsy Research·Nicholas N KopjasPeter R Patrylo
Oct 26, 2005·Neuron·Victoria BalannikYael Stern-Bach
Sep 17, 2008·Neuropharmacology·David E JaneGraham L Collingridge
Mar 24, 2007·Journal of Pharmacological Sciences·Kouichiro MinamiYoichi Ueta
Aug 19, 2017·Journal of Lipid Research·Benjamin Michael DavisM Francesca Cordeiro
Jun 4, 2012·World Journal of Critical Care Medicine·Cheng ZhouXiang-Dong Chen
Dec 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·Akira KitamuraToshio Narahashi
Feb 24, 2006·Pharmacogenetics and Genomics·Jonathan Z PanMaryellen Fazen Eckenhoff
Feb 29, 2020·Current Neuropharmacology·Xuechao HaoCheng Zhou

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.