Table 9.3.

Dopamine receptor heteromers^a

Heteromer pair	Detection techniques	Changes in heteromer properties			References
		Binding	Signaling	Trafficking
D1R–D2R	Co-IP, FRET, protein complementation assay	Not changed	Gαq-mediated signaling by the heteromer	Not reported	125,220–224
D1R–D3R	Co-IP, BRET	↑ Dopamine binding	↑ Dopamine signaling	Heteromer internalized only by agonists to both receptors	225
D1R–A1AR	Co-IP	Not reported	↓ D1R signaling by combination of agonists to both receptors	Not reported	226
D2R–D3R	Co-IP, functional complementation	Not reported	↑ Potency with preferential protomer agonists	Not reported	227,228
D2R–A2AR	Co-IP, BRET, FRET	Not reported	D2R ↓ efficacy and potency of A2AR agonists	Heteromer internalization by agonist to either protomer	219,229–232
D2R–GSHR1a	TR-FRET	Not reported	D2R signals via Gαq and not Gαi	Not reported	233
D2R–NTS1	IP+fluorescence spectroscopy	↓ Affinity for D2R agonist in the presence of NTS1 agonist	↑ Potency of D2R in the presence of NTS1 agonist	NTS1 agonist ↑ D2R internalization	234,235
D2R–OTR	BRET, proximity ligation assays	↑ D2R antagonist binding by low doses of OTR agonist	↑ Efficacy and potency of D2R signaling by OTR agonist	Not reported	236
D2R–SSTR2	Co-IP, pbFRET	Modulation of binding properties of individual protomers	SSTR2 agonist ↑ D2R signaling	D2R agonist ↑ SSTR2 internalization	237
D2R–SSTR5	Functional complementation, pbFRET	↑ Affinity for each protomer agonist	Agonist to one protomer ↑ signaling by agonist to second protomer	Not reported	144
D2R–5-HT2AR	Co-IP	D2R agonist ↑ affinity of 5-HT2AR agonist	D2R agonist ↑ potency of hallucinogenic 5-HT2AR agonist	Not reported	238
D2R–mGluR5–A2AR	Co-IP, BRET+bimolecular fluorescence complementation	Not reported	Not reported	Not reported	127
D4R–α1BAR	Co-IP, BRET	D4R agonist ↓ binding displacement by α1BAR agonist	D4R agonist ↓ α1BAR signaling	Not reported	239
D4R–β1AR	Co-IP, BRET	D4R agonist ↓ binding displacement by β1AR agonist	D4R agonist ↓ β1AR signaling	Not reported	239
D4R–β2AR	Co-IP, BRET	Not reported	Not reported	Not reported	240

^aThis table does not include heteromers involving opioid or cannabinoid receptors. These are described in Tables 9.1 and 9.2.