Table 1.

Ligands modulating MOP-DOP receptor heteromer signalling or trafficking

Ligand	Ligand binding and signalling	Trafficking	References
DAMGO	Induces prolonged ERK1/2 activation that is blocked by β-arrestin-2 siRNA1 Activates Ca2+-mediated signalling2 Binding is increased in the presence of a DOP receptor antagonist3	Internalizes the MOP-DOP receptor heteromer and this is blocked by DOP receptor antagonists4	1Rozenfeld et al., 2007 2Charles et al., 2003 3Gomes et al., 2000 4Milan-Lobo and Whistler, 2011
Methadone	Not reported	Induces internalization and degradation of MOP-DOP receptor heteromer, and this is blocked by DOP receptor antagonists	Milan-Lobo and Whistler, 2011
Deltorphin II	Induces β-arrestin recruitment, and this is blocked by MOP-DOP receptor heteromer-selective antibody5	Induces internalization of MOP-DOP receptor heteromers6	5Gomes et al., 2013b 6Hasbi et al., 2007
DPDPE, DSLET	Not reported	Does not internalize MOP-DOP receptor heteromers	Hasbi et al., 2007
Bivalent ligands (oxymorphone + ENIT, naltrexone+DM-SNC80)	These ligands show low affinity at DOP receptors and enhanced affinity at MOP-DOP receptor heteromers	Not reported	Harvey et al., 2012
Bivalent ligand (MDAN21)	Not reported	Does not internalize MOP-DOP receptor heteromers, and this is reversed by naltrindole.	Yekkirala et al., 2013
Monovalent ligands (MA19, DN20)	Not reported	Combination of these ligands facilitates internalization of MOP-DOP receptor heteromer.	Yekkirala et al., 2013
Biased agonist (CYM51010)	CYM51010 induces both β-arrestin- and G protein-mediated signalling.	Not reported	Gomes et al., 2013b