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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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| Published in: | Molecular pharmacology 2009-06, Vol.75 (6), p.1380-1391 |
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| Main Authors: | , , , , , , , , , , , , , |
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| Language: | English |
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| container_end_page | 1391 |
| container_issue | 6 |
| container_start_page | 1380 |
| container_title | Molecular pharmacology |
| container_volume | 75 |
| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1124/mol.108.054395 |
| format | article |
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| fulltext | fulltext |
| identifier | EISSN: 1521-0111 |
| ispartof | Molecular pharmacology, 2009-06, Vol.75 (6), p.1380-1391 |
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| language | eng |
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| source | Free Full-Text Journals in Chemistry |
| 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 |
| title | Evidence for distinct antagonist-revealed functional states of 5-hydroxytryptamine(2A) receptor homodimers |
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