title: Evidence for distinct antagonist-revealed functional states of 5-hydroxytryptamine(2A) receptor homodimers.
abstract: 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.
authors.affiliation: Departamento de Farmacología, Instituto de Farmacia Industrial, Universidad de Santiago de Compostela, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Brea
authors.forename: Marián
authors.initials: M
authors.lastname: Castro
authors.forename: Jesús
authors.initials: J
authors.lastname: Giraldo
authors.forename: Juan F
authors.initials: JF
authors.lastname: López-Giménez
authors.forename: Juan Fernando
authors.initials: JF
authors.lastname: Padín
authors.forename: Fátima
authors.initials: F
authors.lastname: Quintián
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Cadavid
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Vilaró
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Mengod
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Berg
authors.forename: William P
authors.initials: WP
authors.lastname: Clarke
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vilardaga
authors.forename: Graeme
authors.initials: G
authors.lastname: Milligan
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Loza
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D047468:Immunoprecipitation; D008954:Models, Biological; D011487:Protein Conformation; D055503:Protein Multimerization; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D058830:Serotonin 5-HT2 Receptor Antagonists; D015398:Signal Transduction
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists