%0 Journal Article %A José Brea %A Marián Castro %A Jesús Giraldo %A Juan F. López-Giménez %A Juan Fernando Padín %A Fátima Quintián %A Maria Isabel Cadavid %A Maria Teresa Vilaró %A Guadalupe Mengod %A Kelly A. Berg %A William P. Clarke %A Jean-Pierre Vilardaga %A Graeme Milligan %A Maria Isabel Loza %T Evidence for Distinct Antagonist-Revealed Functional States of 5-Hydroxytryptamine2A Receptor Homodimers %D 2009 %R 10.1124/mol.108.054395 %J Molecular Pharmacology %P 1380-1391 %V 75 %N 6 %X 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. The American Society for Pharmacology and Experimental Therapeutics %U https://molpharm.aspetjournals.org/content/molpharm/75/6/1380.full.pdf