Creative Biogene Creative Biogene
Inquiry
Pages
Products
  1. Home
  2. Search Results for "DRD2"

DRD2

Official Full Name
dopamine receptor D2
Organism
Homo sapiens
GeneID
1813
Background
This gene encodes the D2 subtype of the dopamine receptor. This G-protein coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia. 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. [provided by RefSeq, Jul 2008]
Synonyms
D2R; D2DR;
Bio Chemical Class
GPCR rhodopsin
Protein Sequence
MDPLNLSWYDDDLERQNWSRPFNGSDGKADRPHYNYYATLLTLLIAVIVFGNVLVCMAVSREKALQTTTNYLIVSLAVADLLVATLVMPWVVYLEVVGEWKFSRIHCDIFVTLDVMMCTASILNLCAISIDRYTAVAMPMLYNTRYSSKRRVTVMISIVWVLSFTISCPLLFGLNNADQNECIIANPAFVVYSSIVSFYVPFIVTLLVYIKIYIVLRRRRKRVNTKRSSRAFRAHLRAPLKGNCTHPEDMKLCTVIMKSNGSFPVNRRRVEAARRAQELEMEMLSSTSPPERTRYSPIPPSHHQLTLPDPSHHGLHSTPDSPAKPEKNGHAKDHPKIAKIFEIQTMPNGKTRTSLKTMSRRKLSQQKEKKATQMLAIVLGVFIICWLPFFITHILNIHCDCNIPPVLYSAFTWLGYVNSAVNPIIYTTFNIEFRKAFLKILHC
Open
Disease
Allergic/hypersensitivity disorder, Alzheimer disease, Anxiety disorder, Asthma, Attention deficit hyperactivity disorder, Bacterial infection, Bipolar disorder, Brain cancer, Breast cancer, Breathing abnormality, Carcinoid syndrome, Cardiovascular disease, Cerebral ischaemia, Choreiform disorder, Chronic kidney disease, Chronic obstructive pulmonary disease, Depression, Digestive system disease, Endocrine gland neoplasm, Endometrial cancer, Essential hypertension, Faecal incontinence, Fatigue, Fibrosis, Gangrene, Gastroduodenal motor/secretory disorder, General pain disorder, Glaucoma, Heart failure, Hyperaemia, Hypertension, Hypotension, Idiopathic interstitial pneumonitis, Inborn porphyrin/heme metabolism error, Indeterminate colitis, Insomnia, Intellectual development disorder, Itching, Leukaemia, Lung cancer, Lymphoma, Mental/behavioural/neurodevelopmental disorder, Migraine, Multiple myeloma, Nausea/vomiting, Nicotine use disorder, Pain, Pancreatic cancer, Parkinsonism, Pituitary gland disorder, Postoperative inflammation, Postpartum haemorrhage, Psoriasis, Psychotic disorder, Pulmonary hypertension, Respiratory infection, Restless legs syndrome, Schizoaffective disorder, Schizophrenia, Sexual dysfunction, Solid tumour/cancer, Stomach cancer, Substance abuse, Thrombocytopenia, Thyrotoxicosis, Tonus and reflex abnormality, Type 2 diabetes mellitus, Unspecific substance use disorder
Approved Drug
70 +
Clinical Trial Drug
52 +
Discontinued Drug
47 +

Cat.No. Product Name Price
Cat.No. Product Name Price
Cat.No. Product Name Price
Cat.No. Product Name Tag Price
Cat.No. Product Name Price

Detailed Information

The DRD2 gene on chromosome 11q22-23 comprises 8 exons and 7 introns. Encoding a 415 amino acid protein may be split into two primary isoforms: the long form (D2L) and the short form (D2S). These isoforms fulfill diverse purposes and are expressed in various brain areas. Mostly located in the striatum, nucleus accumbens, and olfactory bulb, D2L is a postsynaptic receptor. It is related to postsynaptic signal modulation. Conversely, D2S controls the release of dopamine from neurons in the ventral tegmental region and the substantia nigra pars compacta by functioning as a presynaptic autoreceptor. The DRD2 receptor's capacity to control dopamine release and activity in different areas of the brain sets it as a major target for antipsychotic medications and Parkinson's disease therapies.

Figure 1 illustrates the signaling pathways activated by the D2 dopamine receptor, including both Gαi/o protein-mediated inhibition of cAMP production and a Beta-arrestin 2 complex that regulates signaling independently of G-protein involvement.Figure 1. The D2 Dopamine Receptor and Its Signaling Pathways. (Bibb JA, 2005)

DRD2-Mediated Signaling Pathways

DRD2 mostly links with the Gαi component of G-proteins, which inhibits adenylyl cyclase (AC) function, therefore lowering the cAMP levels in the cell. This drop in cAMP then reduces the activity of protein kinase A (PKA), a fundamental control mechanism of numerous downstream signaling processes. Through this route, DRD2 alters many ion channels, including those of potassium and calcium, therefore influencing the release of neurotransmitters. For motor control, especially in the basal ganglia where dopamine is essential in controlling movement, this modulation of ion channels has important consequences.

Furthermore, by use of Gβγ subunits, DRD2 may activate the phospholipase C (PLC) pathway. Inositol trisphosphate (IP3) and diacylglycerol (DAG) produced from this activation cause calcium release from intracellular storage and, respectively, activate protein kinase C (PKC). Synaptic plasticity depends on the higher intracellular calcium and activated PKC, which shapes memory and learning processes.

Driven by DRD2, another important mechanism is G-protein inwardly rectifying potassium (GIRK). Once triggered, DRD2 increases GIRK activity, which results in hyperpolarisation of the neuron and decreased neuronal excitability. Maintaining homeostasis in dopaminergic neurons, this mechanism functions as a feedback loop controlling dopamine output.

Apart from conventional G-protein mediated pathways, DRD2 also contributes to G-protein independent signaling. One interesting route is the interaction between DRD2 and arrestins, which function as scaffolding for different signaling complexes. For example, DRD2 may control the AKT/Glycogen synthase kinase 3β (GSK-3β) pathway, which has been linked to mental diseases like bipolar illness and schizophrenia. Under this route, DRD2 reduces AKT activity, thereby activating GSK-3β, a kinase that controls many cellular processes including cell differentiation, metabolism, and death. Hyperactivity seen in certain mental diseases has been connected to disturbance of this circuit.

Additionally, DRD2 has been shown to interact with the Na+/K+ ATPase pump, a necessary control of neuronal resting membrane potential. By changing the excitability of neurons, inhibiting Na+/K+ ATPase emphasizes, even more, the various functions DRD2 performs in neural signaling outside of conventional G-protein processes.

DRD2 in Schizophrenia

The D2S isoform's significance in the development of schizophrenia has lately been highlighted by studies. Although both isoforms are expressed in the brain, the short isoform seems to be more important in the illness. Researchers at Johns Hopkins University found in 2022 that greater schizophrenia risk is linked to varying expression of the D2S isoform but not D2L. This result implies that the function of a presynaptic autoreceptor in the D2S isoform might help to explain the dysregulation of dopamine signaling seen in the condition.

In healthy people, DRD2 helps to control dopamine release, therefore preserving a balance in the dopaminergic system. But in those with schizophrenia, the D2S isoform's malfunction causes inappropriate control of dopamine release, which results in an excess of the neurotransmitter.

DRD2 in Parkinson’s Disease and Addiction

Linked to schizophrenia, DRD2 is also a key component in Parkinson's disease, a neurodegenerative condition that kills substantia nigra dopamine-generating neurons. Dopaminergic neuron loss in Parkinson's disease compromises dopamine signaling in motor control circuits. Dopamine agonists and other DRD2-targeting medications help Parkinson's disease sufferers restore dopaminergic signaling and reduce bradykinesia, tremors, and stiffness. Addiction mechanisms relate to DRD2. Abuse of cocaine and amphetamine increases brain reward circuit dopamine, hence enhancing DRD2 receptors. Strong stimulation over time may desensitize and downregulate receptors, leading to tolerance and addiction.

DRD2 in Cancer

Studies have shown that DRD2 can trigger a form of programmed cell death known as ferroptosis in breast cancer cells. Through its interaction with β-arrestin2, DRD2 downregulates critical proteins such as DDX5 and Eef1a2, ultimately inhibiting the NF-κB signaling pathway, a key player in cancer cell survival. This novel role of DRD2 in promoting cancer cell death has opened up new avenues for research into dopamine receptor agonists as potential adjuvants in cancer therapy.

Apart from breast cancer, first-line therapy for prolactinomas, a kind of pituitary tumor, is already bromocriptine and cabergoline, dopamine receptor agonists. Targeting DRD2 helps these medications lower prolactin production and stop tumor development. Researchers are now looking at whether other cancer types, including breast and colorectal cancer, may benefit from the same tactics.

References:

  1. Benjamin KJM, Chen Q, Jaffe AE, et al. Analysis of the caudate nucleus transcriptome in individuals with schizophrenia highlights effects of antipsychotics and new risk genes. Nat Neurosci. 2022, 25(11):1559-1568.
  2. Tan Y, Sun R, Liu L, et al. Tumor suppressor DRD2 facilitates M1 macrophages and restricts NF-κB signaling to trigger pyroptosis in breast cancer. Theranostics. 2021, 11(11):5214-5231.
  3. Costa R, Santa-Maria CA, Scholtens DM, et al. A pilot study of cabergoline for the treatment of metastatic breast cancer. Breast Cancer Res Treat. 2017, 165(3):585-592.
  4. Bibb JA. Decoding dopamine signaling. Cell. 2005;122(2):153-155.
Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry

Products

Transfected Stable Cell Lines

Premade Virus Particles

Laboratory Equipment

RNA Interference Products

Cell Lysate

Clones

Enzymes

Kits

Aptamers

Services

Stable Cell Line Generation

Target-based Drug Discovery Service

Custom Libraries Construction Service

Microbe Genome Editing Service

Biosafety Testing Service

Nucleotides Service

MicroRNA Service

RNAi Service

Custom Viral Service

Platforms

CRISPR/Cas9 PlatformCB

QvirusTM Platform

IntegrateRNA Platform

Microbiology Platform

Zebrafish Platform

Get in Touch

Tel

Fax

Email

USA

Germany

Copyright © Creative Biogene. All rights reserved.

Privacy Policy | Cookie Policy