The intracellular loop 3 of the D2 receptor contains two adjacent arginine residues, while the carboxyl tail of the D1 receptor possesses two adjacent glutamic acid residues.
The two receptors can form a heteromer complex via a salt bridge between the guanidine moiety and the carboxylic group.
[3] In comparison, signalling of the homologous D5–D2 receptor heteromer involves the influx of extracellular calcium.
Disruption of the heteromer can be achieved either directly by ligands interacting with the cytoplasmic interface, less directly by ligands that target the extracellular binding site, or indirectly as a downstream effect of classical antidepressant treatment.
[5] One study found negative results regarding a shift from Gs/a coupling to Gq/11 signaling; so such dynamics could be mediated by cAMP-dependent cascades rather from phospholipase C regulation.