Back to Search
Start Over
Amino acids in transmembrane domain two influence anesthetic enhancement of serotonin-3A receptor function
- Source :
- Molecular Brain Research. 118:45-51
- Publication Year :
- 2003
- Publisher :
- Elsevier BV, 2003.
-
Abstract
- Alcohols and volatile anesthetics affect the function of members of the nicotinic acetylcholine (nACh) superfamily of receptors. Studies on glycine and GABA(A) receptors implicate amino acid residues within transmembrane (TM) regions two and three of these receptors as critical for alcohol and anesthetic enhancement of receptor function. The serotonin-3 (5-HT(3)) receptor is a member of the nicotinic acetylcholine receptor superfamily, sharing sequence and structural homology with the other members. We tested the hypothesis that amino acids of the 5-HT(3) receptor homologous to those shown to affect alcohol and anesthetic potentiation in GABA(A) and glycine receptors also determine the effects of these compounds on the 5-HT(3) receptor. Six 5-HT(3A) mutant cDNAs were generated by site-directed mutagenesis of two amino acids, phenylalanine-269 (14') and lecucine-270 (15') in transmembrane domain two (TM2). When assayed electrophysiologically in Xenopus oocytes, wild-type 5-HT(3) receptors exhibit enhancement of function by enflurane, halothane, isoflurane, chloroform and ethanol, but not by decanol and propofol. Mutations in transmembrane domain two markedly affected alcohol and anesthetic enhancement of 5-HT(3) receptor function. Some mutations had differential effects on the abilities of the isomers enflurane and isoflurane to potentiate 5-HT(3) receptor function.
- Subjects :
- Serotonin
Phenylalanine
Biology
GABAA-rho receptor
Xenopus laevis
Cellular and Molecular Neuroscience
Leucine
Animals
Amino Acid Sequence
Amino Acids
Receptor
Molecular Biology
Glycine receptor
5-HT receptor
Dose-Response Relationship, Drug
Ethanol
Cell Membrane
Drug Synergism
Protein Structure, Tertiary
Transmembrane domain
Nicotinic acetylcholine receptor
Nicotinic agonist
Biochemistry
Anesthetics, Inhalation
Mutation
Mutagenesis, Site-Directed
Oocytes
Female
Receptors, Serotonin, 5-HT3
Cys-loop receptors
Subjects
Details
- ISSN :
- 0169328X
- Volume :
- 118
- Database :
- OpenAIRE
- Journal :
- Molecular Brain Research
- Accession number :
- edsair.doi.dedup.....b4964efa8e5d37970e95022aa258a652