Dopamine Receptor D2 (DRD2)

Dopamine Receptor D2 (DRD2)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Dopamine Receptor D2 (DRD2)</th>
</tr>
<tr>
<td class="label">Drug Class</td>
<td>Examples</td>
</tr>
<tr>
<td class="label">D2 Agonists</td>
<td>Pramipexole, Ropinirole</td>
</tr>
<tr>
<td class="label">D2 Partial Agonists</td>
<td>Aripiprazole</td>
</tr>
<tr>
<td class="label">Typical Antipsychotics</td>
<td>Haloperidol, Chlorpromazine</td>
</tr>
<tr>
<td class="label">Atypical Antipsychotics</td>
<td>Risperidone, Clozapine</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cardiac" style="color:#ef9a9a">Cardiac</a>, <a href="/wiki/depression" style="color:#ef9a9a">Depression</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">231 edges</a></td>
</tr>
</table>

Introduction

Dopamine Receptor D2 (Drd2) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

This page provides comprehensive information about Dopamine Receptor D2, including its structure, normal function in the nervous system, and its role in neurodegenerative diseases. [@missale1998]

...

Dopamine Receptor D2 (DRD2)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Dopamine Receptor D2 (DRD2)</th>
</tr>
<tr>
<td class="label">Drug Class</td>
<td>Examples</td>
</tr>
<tr>
<td class="label">D2 Agonists</td>
<td>Pramipexole, Ropinirole</td>
</tr>
<tr>
<td class="label">D2 Partial Agonists</td>
<td>Aripiprazole</td>
</tr>
<tr>
<td class="label">Typical Antipsychotics</td>
<td>Haloperidol, Chlorpromazine</td>
</tr>
<tr>
<td class="label">Atypical Antipsychotics</td>
<td>Risperidone, Clozapine</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cardiac" style="color:#ef9a9a">Cardiac</a>, <a href="/wiki/depression" style="color:#ef9a9a">Depression</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">231 edges</a></td>
</tr>
</table>

Introduction

Dopamine Receptor D2 (Drd2) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

This page provides comprehensive information about Dopamine Receptor D2, including its structure, normal function in the nervous system, and its role in neurodegenerative diseases. [@missale1998]

:: infobox infobox-protein [@girault2007]
!Protein Name | Dopamine Receptor D2 (DRD2) [@seeman2007]
!Gene | [DRD2](/proteins/drd2-protein) [@vallone2002]
!UniProt ID | [P14416](https://www.uniprot.org/uniprot/P14416)
!PDB Structure | 6CM4, 7R0H, 7VAB
!Molecular Weight | ~51 kDa (GPCR)
!Subcellular Localization | Cell membrane (GPCR), presynaptic terminals
!Protein Family | Dopamine receptor family (D2-like), GPCR class A
!

Structure

DRD2 exists in two primary splice variants:

DRD2S (short): 414 amino acids, mainly presynaptic

DRD2L (long): 443 amino acids, mainly postsynaptic

Domain Organization:

• N-terminal extracellular domain (aa 1-46): Glycosylated extracellular loops
• Seven transmembrane helices (TM1-TM7): Classic GPCR structure
• Third intracellular loop (aa 156-211): Couples to Gi/o proteins (long isoform)
• C-terminal tail (aa 371-443): Contains cysteine for palmitoylation and membrane anchoring

The D2 receptor has higher affinity for dopamine than D1, allowing distinct signaling at lower dopamine concentrations.

Normal Function

DRD2 mediates inhibitory dopamine signaling:

G-protein Coupling: Couples to Gi/o proteins, inhibiting adenylyl cyclase and reducing cAMP

Presynaptic Autoreceptor: Regulates dopamine synthesis, release, and neuronal firing

Motor Control: Inhibits the indirect pathway in basal ganglia

Reward Modulation: Mediates aversive aspects of dopamine signaling

Prolactin Regulation: Inhibits prolactin release from the pituitary

Role in Disease

Parkinson's Disease

• Therapeutic Target: D2/D3 agonists (pramipexole, ropinirole, rotigotine) are first-line treatments
• Motor Symptoms: D2 activation improves bradykinesia and rigidity
• Motor Complications: Long-term use associated with dyskinesias and motor fluctuations

Schizophrenia

• D2 Blockade: Classic antipsychotics (haloperidol, risperidone) primarily block D2 receptors
• Positive Symptoms: D2 antagonism reduces hallucinations and delusions
• EPS: D2 blockade in striatum causes extrapyramidal side effects
• Atypical Antipsychotics: Lower D2 affinity, also target 5-HT2 receptors

Huntington's Disease

• D2 Receptor Loss: Progressive decline in D2 receptor binding in striatum
• Motor Symptoms: Contributes to chorea and dystonia

Prolactinoma

• D2 Agonists: Bromocriptine, cabergoline used to treat prolactin-secreting pituitary adenomas

Therapeutic Targeting

Key Publications

Beaulieu JM, Gainetdinov RR. (2011) "The physiology, signaling, and pharmacology of dopamine receptors." Pharmacol Rev 63:182-217. [DOI:10.1124/pr.110.002642](https://doi.org/10.1124/pr.110.002642)

Mailman R, et al. (2000) "Functional effects of dopamine receptor agonists." Adv Pharmacol 47:53-87.

Strange PG. (2008) "Signaling mechanisms of D2 dopamine receptors." Adv Pharmacol 55:37-52.

Seeman P. (2013) "Schizophrenia and dopamine receptors." Eur Neuropsychopharmacol 23:999-1009.

Background

The study of Dopamine Receptor D2 (Drd2) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• [Parkinson's Disease](/diseases/parkinsons-disease) Disease page
• Schizophrenia - Disease page
• Huntington's Disease - Disease page
• DRD2 Gene - Gene page
• Dopamine Signaling - Mechanism
• Basal Ganglia - Brain region

External Links

• [UniProt P14416](https://www.uniprot.org/uniprot/P14416)
• [OMIM 126450](https://www.omim.org/entry/126450)
• [GeneCards DRD2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=DRD2)
• [IUPHAR Database](https://www.guidetopharmacology.org/GTORL1957)

References

[@missale1998]: Missale C, et al. (1998). D2 receptor isoforms. Physiol Rev. PMID: 9720590(https://pubmed.ncbi.nlm.nih.gov/9720590/)
[@girault2007]: Girault JA, et al. (2007). D2 receptors in basal ganglia. Nat Rev Neurosci. PMID: 17559332(https://pubmed.ncbi.nlm.nih.gov/17559332/)
[@seeman2007]: Seeman P. (2007). Dopamine D2 receptors. Am J Psychiatry. PMID: 17606634(https://pubmed.ncbi.nlm.nih.gov/17606634/)
[@vallone2002]: Vallone D, et al. (2002). D2 receptors and behavior. Neurosci Biobehav Rev. PMID: 11856549(https://pubmed.ncbi.nlm.nih.gov/11856549/)

See Also

• [DRD2 Gene](/drd2-gene)
• [Dopamine Receptors](/dopamine-receptors)
• [G-Protein Coupled Receptors](/g-protein-coupled-receptors)

External Links

• [DRD2 Protein - UniProt](https://www.uniprot.org/uniprot/P14416)