D1–D2 dopamine receptor heteromer

Dopamine receptor D1
Identifiers
Symbol	DRD1
Entrez	1812
HUGO	3020
OMIM	126449
RefSeq	NP_000785
UniProt	P21728
Other data
Locus	Chr. 5 q35.2

Dopamine receptor D2
Identifiers
Symbol	DRD2
Entrez	1813
HUGO	3023
OMIM	126450
RefSeq	NP_000786
UniProt	P14416
Other data
Locus	Chr. 11 q22

The D₁–D₂ dopamine receptor heteromer is a receptor heteromer consisting of D₁ and D₂ protomers.

Structure

D₁ and D₂ receptors interact primarily through discrete amino acids in the cytoplasmic regions of each receptor, with no involvement of transmembrane parts. 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.

Signal transduction

The signalling of the D₁–D₂ receptor heteromer is distinct from that of the parent receptor monomers. It comprises G_q/11 coupling, phospholipase C activation, intracellular calcium release from inositol trisphosphate receptor-sensitive stores, CaMKII activation and BDNF production. In comparison, signalling of the homologous D₅–D₂ receptor heteromer involves the influx of extracellular calcium.

Physiology

The D₁–D₂ receptor is upregulated in individuals suffering from major depression, and especially the ratio D₁–D₂ to D₁ receptor is markedly shifted towards the heteromer. Counteracting this upregulation decreases depressive symptoms. 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.

Ligands

• SKF-83,959