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Br J Pharmacol
2006 May 01;1481:88-101. doi: 10.1038/sj.bjp.0706685.
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Mutations of L293 in transmembrane two of the mouse 5-hydroxytryptamine3A receptor alter gating and alcohol modulatory actions.
Hu XQ
,
Hayrapetyan V
,
Gadhiya JJ
,
Rhubottom HE
,
Lovinger DM
,
Machu TK
.
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1 The goal of this study was to determine whether mutations of L293 at the 15' position of TM2 in the 5-HT(3A) receptor alter macroscopic current kinetics, and if these changes could account for alterations in alcohol modulation. Receptor function was assessed in Xenopus oocytes under voltage-clamp and in HEK293 cells with whole-cell patch-clamp recording and rapid drug application. 2 Examination of responses of L293C and L293S receptors to agonist alone revealed enhanced activation, deactivation, and desensitization rates relative to the wild-type receptor. The L293G mutation produced marked slowing of deactivation and desensitization rates. Increased potency of 5-HT and increased efficacy of the partial agonist, DA, was also observed in these mutant receptors. 3 Ethanol and trichloroethanol (TCEt) enhancement of receptor function was reduced or eliminated in receptors containing L293 mutations to C, G, or S. The L293I mutant receptor retained ethanol and TCEt sensitivity. Ethanol and TCEt enhanced activation rate in the wild-type, but not the L293G and L293S receptors. No relationship was observed between any physicochemical property of the substituted amino acids and the change in alcohol potentiation of function. 4 The changes in receptor-channel properties in the mutant receptors support the idea that the L293 residue has important roles in channel gating. Our findings indicate that loss of allosteric modulation by alcohols is not related in any simple way to changes in channel kinetic properties brought about by L293 mutants. We did not observe any evidence that L293 is part of an alcohol binding site.
Belelli,
The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid.
1997, Pubmed,
Xenbase
Belelli,
The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid.
1997,
Pubmed
,
Xenbase
Davies,
The 5-HT3B subunit is a major determinant of serotonin-receptor function.
1999,
Pubmed
,
Xenbase
Derkach,
5-HT3 receptors are membrane ion channels.
1989,
Pubmed
Dubin,
The pharmacological and functional characteristics of the serotonin 5-HT(3A) receptor are specifically modified by a 5-HT(3B) receptor subunit.
1999,
Pubmed
,
Xenbase
Findlay,
Allosteric modulation in spontaneously active mutant gamma-aminobutyric acidA receptors.
2001,
Pubmed
,
Xenbase
Forman,
Novel modulation of a nicotinic receptor channel mutant reveals that the open state is stabilized by ethanol.
1999,
Pubmed
,
Xenbase
Hayrapetyan,
Co-expression of the 5-HT(3B) subunit with the 5-HT(3A) receptor reduces alcohol sensitivity.
2005,
Pubmed
Hopp,
Prediction of protein antigenic determinants from amino acid sequences.
1981,
Pubmed
Jenkins,
Actions of general anaesthetics on 5-HT3 receptors in N1E-115 neuroblastoma cells.
1996,
Pubmed
Johnson,
Attenuation of some alcohol-induced mood changes and the desire to drink by 5-HT3 receptor blockade: a preliminary study in healthy male volunteers.
1993,
Pubmed
Karnovsky,
A cluster of novel serotonin receptor 3-like genes on human chromosome 3.
2003,
Pubmed
Kelley,
A cytoplasmic region determines single-channel conductance in 5-HT3 receptors.
2003,
Pubmed
Knapp,
Zacopride, a 5-HT3 receptor antagonist, reduces voluntary ethanol consumption in rats.
1992,
Pubmed
Koltchine,
Agonist gating and isoflurane potentiation in the human gamma-aminobutyric acid type A receptor determined by the volume of a second transmembrane domain residue.
1999,
Pubmed
Kyte,
A simple method for displaying the hydropathic character of a protein.
1982,
Pubmed
Lopreato,
Amino acids in transmembrane domain two influence anesthetic enhancement of serotonin-3A receptor function.
2003,
Pubmed
,
Xenbase
Lovinger,
Ethanol potentiation of 5-hydroxytryptamine3 receptor-mediated ion current in neuroblastoma cells and isolated adult mammalian neurons.
1991,
Pubmed
Lovinger,
Ethanol and trichloroethanol alter gating of 5-HT3 receptor-channels in NCB-20 neuroblastoma cells.
2000,
Pubmed
Lovinger,
Trichloroethanol potentiation of 5-hydroxytryptamine3 receptor-mediated ion current in nodose ganglion neurons from the adult rat.
1993,
Pubmed
Machu,
Alcohols and anesthetics enhance the function of 5-hydroxytryptamine3 receptors expressed in Xenopus laevis oocytes.
1994,
Pubmed
,
Xenbase
Maricq,
Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel.
1991,
Pubmed
,
Xenbase
Mascia,
Specific binding sites for alcohols and anesthetics on ligand-gated ion channels.
2000,
Pubmed
,
Xenbase
McBride,
Serotonin-3 receptors in the actions of alcohol, alcohol reinforcement, and alcoholism.
2004,
Pubmed
Mihic,
Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors.
1997,
Pubmed
,
Xenbase
Morales,
Differential composition of 5-hydroxytryptamine3 receptors synthesized in the rat CNS and peripheral nervous system.
2002,
Pubmed
Mott,
Open probability of homomeric murine 5-HT3A serotonin receptors depends on subunit occupancy.
2001,
Pubmed
,
Xenbase
Niesler,
Cloning, physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C, HTR3D and HTR3E.
2003,
Pubmed
Panicker,
Evidence for a centrally located gate in the pore of a serotonin-gated ion channel.
2002,
Pubmed
,
Xenbase
Reeves,
Structural and electrostatic properties of the 5-HT3 receptor pore revealed by substituted cysteine accessibility mutagenesis.
2001,
Pubmed
Scheller,
Coupled and uncoupled gating and desensitization effects by pore domain mutations in GABA(A) receptors.
2002,
Pubmed
Sessoms-Sikes,
A mutation in transmembrane domain II of the 5-hydroxytryptamine(3A) receptor stabilizes channel opening and alters alcohol modulatory actions.
2003,
Pubmed
,
Xenbase
Thompson,
Mutation at the putative GABA(A) ion-channel gate reveals changes in allosteric modulation.
1999,
Pubmed
,
Xenbase
van Hooft,
Selection of distinct conformational states of the 5-HT3 receptor by full and partial agonists.
1996,
Pubmed
Wick,
Mutations of gamma-aminobutyric acid and glycine receptors change alcohol cutoff: evidence for an alcohol receptor?
1998,
Pubmed
,
Xenbase
Yamakura,
Amino acid volume and hydropathy of a transmembrane site determine glycine and anesthetic sensitivity of glycine receptors.
1999,
Pubmed
,
Xenbase
Ye,
Enhancement of glycine receptor function by ethanol is inversely correlated with molecular volume at position alpha267.
1998,
Pubmed
,
Xenbase
Zamyatnin,
Protein volume in solution.
1972,
Pubmed
Zhou,
Alcohols potentiate the function of 5-HT3 receptor-channels on NCB-20 neuroblastoma cells by favouring and stabilizing the open channel state.
1998,
Pubmed
Zimmerman,
The characterization of amino acid sequences in proteins by statistical methods.
1968,
Pubmed
