G protein-coupled receptor hetero-dimerization: contribution to pharmacology and function

Br J Pharmacol. 2009 Sep;158(1):5-14. doi: 10.1111/j.1476-5381.2009.00169.x. Epub 2009 Mar 20.


The concept that G protein-coupled receptors (GPCRs) can form hetero-dimers or hetero-oligomers continues to gain experimental support. However, with the exception of the GABA(B) receptor and the sweet and umami taste receptors few reported examples meet all of the criteria suggested in a recent International Union of Basic and Clinical Pharmacology sponsored review (Pin et al., 2007) that should be required to define distinct and physiologically relevant receptor species. Despite this, there are many examples in which pairs of co-expressed GPCRs reciprocally modulate their function, trafficking and/or ligand pharmacology. Such data are at least consistent with physical interactions between the receptor pairs. In recent times, it has been suggested that specific GPCR hetero-dimer or hetero-oligomer pairs may represent key molecular targets of certain clinically effective, small molecule drugs and there is growing interest in efforts to identify ligands that may modulate hetero-dimer function selectively. The current review summarizes key recent developments in these topics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Ligands
  • Protein Multimerization / physiology*
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, G-Protein-Coupled / physiology*


  • Ligands
  • Receptors, G-Protein-Coupled