D2 receptor

D2 receptor

Dopamine receptor D2
1I15.
Available structures
PDB Ortholog search: RCSB
Identifiers
DRD2 Gene
RNA expression pattern

Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene.

Function

This gene encodes the D2 subtype of the dopamine receptor. This G protein-coupled receptor inhibits adenylyl cyclase activity.

Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing.[1]

In mice, regulation of D2R surface expression by the calcium sensor NCS-1 in the dentate gyrus controls exploration, synaptic plasticity and memory formation.[2]

Genetics

Allelic variants:

  • A-241G
  • C132T, G423A, T765C, C939T, C957T, and G1101A[3]
  • Cys311Ser
  • -141C insertion/deletion[4] The polymorphisms has been investigated with respect to association with schizophrenia.[5]

Some researchers have previously associated the polymorphism Taq 1A (rs1800497) to the DRD2 gene. However, the polymorphism resides in exon 8 of the ANKK1 gene.[6]

Ligands

Most of the older antipsychotic drugs such as chlorpromazine and haloperidol are antagonists for the dopamine D2 receptor, but are, in general, very unselective, at best selective only for the "D2-like family" receptors and so binding to D2, D3 and D4, and often also to many other receptors such as those for serotonin and histamine, resulting in a range of side-effects and making them poor agents for scientific research. In similar manner, older dopamine agonists used for Parkinson's disease such as bromocriptine and cabergoline are poorly selective for one dopamine receptor over another, and, although most of these agents do act as D2 agonists, they affect other subtypes as well. Several selective D2 ligands are, however, now available, and this number is likely to increase as further research progresses.

Agonists

Antagonists

D2Sh selective (presynaptic autoreceptors)

Allosteric modulators

  • PAOPA[11]
  • SB-269,652 - allosteric antagonist at dopamine D2 and D3 receptors[12]

Protein-protein interactions

The dopamine receptor D2 has been shown to interact with EPB41L1,[13] PPP1R9B[14] and NCS-1.[15]

Receptor oligomers

The D2 receptor forms heteromers with the following receptors: dopamine D1 (→ D1-D2),[16] D3,[17] 5-HT2A,[18] adenosine A2A,[19] CB1, mGlu5.

See also

References

Further reading

External links

  • Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.