G protein-coupled receptor heteromers as new targets for drug development

Prog Mol Biol Transl Sci. 2010;91:41-52. doi: 10.1016/S1877-1173(10)91002-8.


We now have a significant amount of experimental evidence that indicates that G protein-coupled receptor (GPCR) oligomerization, including homo- and heteromerization, is a general phenomenon. Receptor heteromers possess unique biochemical characteristics that are demonstrably different from those of its individual units. These properties include allosteric modulation(s) between units, changes in ligand recognition, G protein-coupling and trafficking. The discovery of GPCR oligomers have been related to the parallel discovery and application of a variety of resonance energy transfer (RET) techniques, such as bioluminescence, fluorescence and sequential RET (BRET, FRET and SRET, respectively), time-resolved FRET (T-FRET) and fluorescence recovery after photobleaching (FRAP) microscopy. However, RET techniques are difficult to implement in native tissues. For receptor heteromers, indirect approaches, such as the determination of a unique biochemical characteristic ("biochemical fingerprint"), permit their identification in native tissues and their use as targets for drug development. Dopamine and opioid receptor heteromers are the focus of intense research which is related to the possible multiple applications of their putative ligands in pathological conditions, which include basal ganglia disorders, schizophrenia and drug addiction.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Discovery*
  • Energy Transfer
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Luminescent Measurements
  • Protein Structure, Quaternary
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / drug effects*
  • Receptors, G-Protein-Coupled / metabolism


  • Receptors, G-Protein-Coupled