Evidence for distinct antagonist-revealed functional states of 5-hydroxytryptamine(2A) receptor homodimers
| Autor: | Graeme Milligan, Kelly A. Berg, Juan F. López-Giménez, María Isabel Cadavid, Jean-Pierre Vilardaga, Marián Castro, María Isabel Loza, Juan Fernando Padín, José Brea, Jesús Giraldo, Fátima Quintián, William P. Clarke, Guadalupe Mengod, M T Vilaró |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Protein Conformation
5-HT2A receptor Immunoprecipitation medicine.drug_class Pharmacology Biology Models Biological Cell Line Cricetulus Cricetinae Dopamine receptor D2 Fluorescence Resonance Energy Transfer medicine Serotonin 5-HT2 Receptor Antagonists Animals Humans Receptor Serotonin 5-HT2A Receptor Clozapine Typical antipsychotic Molecular Medicine Protein Multimerization Signal transduction Signal Transduction medicine.drug |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | et al. 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-HT2A -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-HT2A receptor-mediated functions in a pathway-specific manner, explained here by a new model of multiple active interconvertible conformations at dimeric receptors. This work was supported by the Ministerio de Educación y Ciencia, Spain [Grants SAF2007-65913, SAF2005-08025-C03]; the Xunta de Galicia [Grant PGIDIT06PXID203186PR, 2007/118]; and by Red Temática de Investigación Cooperativa COMBIOMED from Instituto de Salud Carlos III and Fundació La Marató de TV3 [Reference 070530]. |
| Databáze: | OpenAIRE |
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