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The role of residues in binding loop A in desflurane and propofol modulation of recombinant 5-HT3A receptor

 Bon Nyeo Koo  ;  Mi Kyeong Kim  ;  Jay Yang  ;  Kyeong Tae Min 
 NEUROSCIENCE LETTERS, Vol.465(2) : 147-150, 2009 
Journal Title
Issue Date
Amino Acid Sequence ; Anesthetics, Inhalation/administration & dosage ; Anesthetics, Inhalation/pharmacology* ; Anesthetics, Intravenous/administration & dosage ; Anesthetics, Intravenous/pharmacology* ; Animals ; Binding Sites/genetics ; Dose-Response Relationship, Drug ; Isoflurane/administration & dosage ; Isoflurane/analogs & derivatives* ; Isoflurane/pharmacology ; Membrane Potentials/drug effects ; Membrane Potentials/physiology ; Mice ; Patch-Clamp Techniques ; Point Mutation ; Propofol/administration & dosage ; Propofol/pharmacology* ; Receptors, Serotonin, 5-HT3/genetics ; Receptors, Serotonin, 5-HT3/metabolism* ; Recombinant Proteins/metabolism ; Serotonin/metabolism ; Serotonin 5-HT3 Receptor Antagonists ; Serotonin Antagonists/administration & dosage ; Serotonin Antagonists/pharmacology ; Xenopus laevis
5-HT3A ; Desflurane ; Propofol ; Extracellular domain ; Allosteric modulation
5-Hydroxytryptamine type 3 (5-HT(3)) receptor is modulated by general anesthetics and regarded as a possible site of anesthetic adverse action. Although two amino acids located in transmembrane (TM) 2 and TM3 of LGICs were reported as critical for allosteric modulation by anesthetics and alcohols, other residues could regulate anesthetic modulation. Earlier studies identified the role of glutamate 129 and phenylalanine 130 in the non-TM extracellular region in the agonist binding and coupling in the 5-HT(3A) receptor. We investigated whether these non-TM amino acids are involved in desflurane and propofol modulation of the 5-HT(3A) receptor in mutant 5-HT(3A) receptors (mutants) expressed in Xenopus laevis oocytes. E129D and F130Y mutants were functionally expressed but E129Y and F130S mutants were not gated by serotonin. The wild type and F130Y mutants demonstrated positive modulation by desflurane at 6 and 12vol.%. In contrast, E129D mutants were inhibited by desflurane in a concentration dependent manner. Propofol (1-100 microM) demonstrated depression of the currents in all receptors examined. These findings suggest the role of non-TM residues in the extracellular domain in the anesthetic modulation of the 5-HT(3A) receptor
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Koo, Bon-Nyeo(구본녀) ORCID logo https://orcid.org/0000-0002-3189-1673
Kim, Mi Kyeong(김미경)
Min, Kyeong Tae(민경태) ORCID logo https://orcid.org/0000-0002-3299-4500
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