Evidence for distinct antagonist-revealed functional states of 5-HT2A receptor homodimers

Brea, J.H. et al. (2009) Evidence for distinct antagonist-revealed functional states of 5-HT2A receptor homodimers. Molecular Pharmacology, 75(6), pp. 1380-1391. (doi: 10.1124/mol.108.054395)

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Publisher's URL: http://dx.doi.org/10.1124/mol.108.054395


The serotonin (5-hydroxytryptamine, or 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 FRET and immunoprecipitation studies that the 5-HT2A-receptor homo-dimerized 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

Item Type:Articles
Glasgow Author(s) Enlighten ID:Milligan, Professor Graeme
Authors: Brea, J.H., Castro, M., Giraldo, J., López-Giménez, J.F., Padín, J.F., Quintián, F., Cadavid, M.I., Vilaró, T., Mengod, G., Berg, K. A., Clarke, W.P., Vilardaga, J.P., Milligan, G., and Loza, M.I.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
Q Science > QH Natural history > QH301 Biology
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Molecular Pharmacology

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