D2 Dopamine Receptor Antibodies

The dopamine D₂ receptor (D₂R), encoded by DRD2, is a class A G protein-coupled receptor activated by the endogenous neurotransmitter dopamine. It couples predominantly to Gi/o, inhibiting adenylyl cyclase and modulating potassium and calcium channels. D₂R is abundant in the striatum and is also expressed in midbrain dopaminergic neurons and anterior pituitary lactotrophs. Alternative splicing produces short (D₂S) and long (D₂L) isoforms, with D₂S preferentially associated with presynaptic autoreceptor function and D₂L with postsynaptic signaling. Presynaptic D₂ autoreceptors provide feedback inhibition of dopamine synthesis and release, while postsynaptic D₂R signaling in the striatum helps regulate movement. In the anterior pituitary, D₂R activation suppresses prolactin secretion. Agonist exposure can promote β-arrestin recruitment and receptor internalization, with the extent of these responses depending on the ligand and cellular context. D₂R antagonists such as haloperidol and partial agonists such as aripiprazole are used clinically to treat schizophrenia. D₂-like receptor agonists are also used in Parkinson’s disease, and cabergoline is used to treat hyperprolactinemia.. D2 desensitization, β-arrestin recruitment and signaling are regulated by phosphorylation of third intracellular loop serine317/threonine318 (pS317/pT318-D2). This nomenclature refers to the human D2. Agonist-induced D2 phosphorylation is primarily mediated by GRK2 and GRK3. The development β-arrestin biased D2 ligands has been proposed as strategy for antipsychotics with fewer side effects. Phosphosite-specific antibodies can provide precise information about partial, full and biased agonism of D2 ligands. For more information on D2 receptor pharmacology please refer to the IUPHAR database. For further reading refer to:

Mann A, Keen AC, Mark H, Dasgupta P, Javitch JA, Canals M, Schulz S, Robert Lane J. New phosphosite-specific antibodies to unravel the role of GRK phosphorylation in dopamine D2 receptor regulation and signaling. Sci Rep. 2021 Apr 15;11(1):8288. doi: 10.1038/s41598-021-87417-2. PMID: 33859231; PMCID: PMC8050214.

Beaulieu JM, Gainetdinov RR. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev. 2011 Mar;63(1):182-217. doi:10.1124/pr.110.002642. Epub 2011 Feb 8. Review. PubMed PMID: 21303898.

Beaulieu JM, Espinoza S, Gainetdinov RR. Dopamine receptors - IUPHAR Review 13. Br J Pharmacol. 2015 Jan;172(1):1-23. Review. PubMed PMID: 25671228; PubMed Central PMCID: PMC4280963.