Heterodimers of G protein-coupled receptors as novel and distinct drug targets

G protein-coupled receptors (GPCRs) exist as homodimers and also associate with other GPCRs to form heterodimers. This association may alter the function of both receptors, yielding a distinct functional unit with novel properties. The multiple combinations of GPCR heterodimers, the tissue-selective expression of these complexes and their differential activation offer an exciting perspective for the development of tissue- and receptor-subtype-selective drugs. In this review, we will discuss the evidence available till date for the occurrence of GPCR heterodimerization, particularly in vivo, and describe strategies that can be used for the development of heterodimer-selective ligands.

Section editors:David Sibley – National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, USAC. Anthony Altar – Psychiatric Genomics, Gaithersburg, USATheresa Branchek – Lundbeck Research, Paramus, USA