TY - JOUR
T1 - Evidence for distinct antagonist-revealed functional states of 5-hydroxytryptamine2A receptor homodimers
AU - Brea, José
AU - Castro, Marián
AU - Giraldo, Jesús
AU - López-Giménez, Juan F.
AU - Padín, Juan Fernando
AU - Quintián, Fátima
AU - Cadavid, Maria Isabel
AU - Vilaró, Maria Teresa
AU - Mengod, Guadalupe
AU - Berg, Kelly A.
AU - Clarke, William P.
AU - Vilardaga, Jean Pierre
AU - Milligan, Graeme
AU - Loza, Maria Isabel
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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. Copyright © 2009 The American Society for Pharmacology and Experimental Therapeutics.
AB - 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. Copyright © 2009 The American Society for Pharmacology and Experimental Therapeutics.
U2 - 10.1124/mol.108.054395
DO - 10.1124/mol.108.054395
M3 - Article
SN - 0026-895X
VL - 75
SP - 1380
EP - 1391
JO - Molecular Pharmacology
JF - Molecular Pharmacology
IS - 6
ER -