Evidence for distinct antagonist-revealed functional states of 5-hydroxytryptamine(2A) receptor homodimers

The serotonin (5-hydroxytryptamine; 5-HT) 2A receptor is a cell surface class A G protein-coupled receptor that regulates a multitude of physiological functions of the body and is a target for antipsychotic drugs. Here we found by means of fluorescence resonance energy transfer and immunoprecipitati...

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Bibliographic Details
Published in:	Molecular pharmacology Vol. 75; no. 6; p. 1380
Main Authors:	Brea, José, Castro, Marián, Giraldo, Jesús, López-Giménez, Juan F, Padín, Juan Fernando, Quintián, Fátima, Cadavid, Maria Isabel, Vilaró, Maria Teresa, Mengod, Guadalupe, Berg, Kelly A, Clarke, William P, Vilardaga, Jean-Pierre, Milligan, Graeme, Loza, Maria Isabel
Format:	Journal Article
Language:	English
Published:	United States 01-06-2009
Subjects:	Animals Cell Line Cricetinae Cricetulus Fluorescence Resonance Energy Transfer Humans Immunoprecipitation Models, Biological Protein Conformation Protein Multimerization Receptor, Serotonin, 5-HT2A - physiology Serotonin 5-HT2 Receptor Antagonists Signal Transduction
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Summary:	The serotonin (5-hydroxytryptamine; 5-HT) 2A receptor is a cell surface class A G protein-coupled receptor that regulates a multitude of physiological functions of the body and is a target for antipsychotic drugs. Here we found by means of fluorescence resonance energy transfer and immunoprecipitation studies that the 5-HT(2A)-receptor homodimerized in live cells, which we linked with its antagonist-dependent fingerprint in both binding and receptor signaling. Some antagonists, like the atypical antipsychotics clozapine and risperidone, differentiate themselves from others, like the typical antipsychotic haloperidol, antagonizing these 5-HT(2A) receptor-mediated functions in a pathway-specific manner, explained here by a new model of multiple active interconvertible conformations at dimeric receptors.
ISSN:	1521-0111
DOI:	10.1124/mol.108.054395