Evidence for distinct antagonist-revealed functional states of 5-hydroxytryptamine<inf>2A</inf> receptor homodimers

José Brea, Marián Castro, Jesús Giraldo, Juan F. López-Giménez, Juan Fernando Padín, Fátima Quintián, Maria Isabel Cadavid, Maria Teresa Vilaró, Guadalupe Mengod, Kelly A. Berg, William P. Clarke, Jean Pierre Vilardaga, Graeme Milligan, Maria Isabel Loza

Research output: Contribution to journalArticleResearchpeer-review

49 Citations (Scopus)

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-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.
Original languageEnglish
Pages (from-to)1380-1391
JournalMolecular Pharmacology
Volume75
Issue number6
DOIs
Publication statusPublished - 1 Jan 2009

Fingerprint

Dive into the research topics of 'Evidence for distinct antagonist-revealed functional states of 5-hydroxytryptamine<inf>2A</inf> receptor homodimers'. Together they form a unique fingerprint.

Cite this