Document Detail

The 5-HT3B subunit confers spontaneous channel opening and altered ligand properties of the 5-HT3 receptor.
MedLine Citation:
PMID:  18187416     Owner:  NLM     Status:  MEDLINE    
Current receptor theory suggests that there is an equilibrium between the inactive (R) and active (R*) conformations of ligand-gated ion channels and G protein-coupled receptors. The actions of ligands in both receptor types could be appropriately explained by this two-state model. Ligands such as agonists and antagonists affect receptor function by stabilizing one or both conformations. The 5-HT3 receptor is a member of the Cys-loop ligand-gated ion channel superfamily participating in synaptic transmission. Here we show that co-expression of the 5-HT3A and 5-HT3B receptor subunits in the human embryonic kidney (HEK) 293 cells results in a receptor that displays a low level of constitutive (or agonist-independent) activity. Furthermore, we also demonstrate that the properties of ligands can be modified by receptor composition. Whereas the 5-hydroxytryptamine (5-HT) analog 5-methoxyindole is a partial agonist at the 5-HT3A receptor, it becomes a "protean agonist" (functioning as an agonist and an inverse agonist at the same receptor) at the 5-HT3AB receptor (after the Greek god Proteus, who was able to change his shape and appearance at will). In addition, the 5-HT analog 5-hydroxyindole is a positive allosteric modulator for the liganded active (AR*) conformation of the 5-HT3A and 5-HT3AB receptors and a negative allosteric modulator for the spontaneously active (R*) conformation of the 5-HT3AB receptor, suggesting that the spontaneously active (R*) and liganded active (AR*) conformations are differentially modulated by 5-hydroxyindole. Thus, the incorporation of the 5-HT3B subunit leads to spontaneous channel opening and altered ligand properties.
Xiang-Qun Hu; Robert W Peoples
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-01-10
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-03-10     Completed Date:  2008-05-20     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6826-31     Citation Subset:  IM    
Department of Biomedical Sciences, College of Health Sciences, Marquette University, Milwaukee, Wisconsin 53201-1881, USA.
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MeSH Terms
Cell Line
Cell Physiological Phenomena
DNA, Complementary / metabolism
Indoles / pharmacology
Models, Biological
Models, Chemical
Patch-Clamp Techniques
Protein Binding
Protein Conformation
Receptors, Serotonin, 5-HT3 / chemistry*,  metabolism*
Grant Support
Reg. No./Substance:
0/DNA, Complementary; 0/Indoles; 0/Ligands; 0/Receptors, Serotonin, 5-HT3; 1006-94-6/5-methoxyindole

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