Opioid and chemokine receptor heterodimers: arranged marriages or dangerous liaisons?

Heterodimerization of GPCRs (G-protein-coupled receptors) has begun to be appreciated as a rich new vein for drug discovery. The possibility of developing modulators for different GPCRs which work at allosteric sites other than the ligand-binding site is not new, but the notion of using a dimeric receptor partner as the target for this intervention has not yet percolated into the broader industrial community. In the present article, I discuss this notion in the context of the heterodimeric δ-opioid receptor–CXCR2 chemokine receptor dimer identified by Parenty et al., in this issue of the Biochemical Journal.