Dopamine receptor D2
Encyclopedia
Dopamine receptor D2, also known as D2R, is a protein
that, in humans, is encoded by the DRD2 gene
.
. 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.
The polymorphisms has been investigated with respect to association with schizophrenia
.
Some researchers have previously associated the polymorphism
Taq 1A (rs1800497) to the DRD2 gene.
However, the polymorphism sits in exon
8 of the ANKK1
gene.
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.
D2Sh selective (presynaptic autoreceptors)
with Adenosine A2A receptor
, EPB41L1
and PPP1R9B
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that, in humans, is encoded by the DRD2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
This gene encodes the D2 subtype of the dopamine receptorDopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
. This G protein-coupled receptor
G protein-coupled receptor
G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
inhibits adenylyl cyclase activity. A missense mutation
Missense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...
in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.
Alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA 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.
Genetics
Allelic variants:- A-241G
- C132T, G423A, T765C, C939T, C957TC957TThe C957T gene polymorphism is a synonymous mutation located within the 957th base pair of the DRD2 gene. This base pair is located in exon 7. Most synonymous mutations are silent. However, the C957T mutation is an exception to this rule. While the 957C allele codes for the same polypeptide as the...
, and G1101A - Cys311Ser
- -141C insertion/deletion
The polymorphisms has been investigated with respect to association with schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.
Some researchers have previously associated the polymorphism
Polymorphism
Polymorphism or dimorphism may refer to:-Biology:* Polymorphism , including:** having multiple phenotypes within a population; the switch that determines which phenotype an individual displays can be genetic or environmental...
Taq 1A (rs1800497) to the DRD2 gene.
However, the polymorphism sits in exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
8 of the ANKK1
ANKK1
The ANKK1 gene is a member of an extensive family of proteins involved in signal transduction pathways. This gene contains a single nucleotide polymorphism that causes an amino acid substitution within the 11th of 12 ankyrin repeats of ANKK1...
gene.
Ligands
Most of the older antipsychoticAntipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
drugs such as chlorpromazine
Chlorpromazine
Chlorpromazine is a typical antipsychotic...
and haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
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
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
and histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
, 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
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
such as bromocriptine
Bromocriptine
Bromocriptine , an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease , hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.- Indications :Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly...
and cabergoline
Cabergoline
Cabergoline , an ergot derivative, is a potent dopamine receptor agonist on D2 receptors. In vitro, rat studies show cabergoline has a direct inhibitory effect on pituitary lactotroph cells...
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
- AplindoreAplindoreAplindore is a drug which acts as a partial agonist selective for the dopamine receptor D2. It is being developed by the pharmaceutical company Neurogen as a treatment for Parkinson's disease and restless legs syndrome....
- partial agonist - AripiprazoleAripiprazoleAripiprazole is an atypical antipsychotic and antidepressant used in the treatment of schizophrenia, bipolar disorder, and clinical depression...
(Abilify in USA) - partial agonist - GSK-789,472GSK-789,472GSK-789,472 is a drug which acts as both a potent and selective partial agonist at the dopamine receptor D2, as well as an antagonist at the related D3 subtype, but with good selectivity over D4 and other unrelated receptors....
- mixed D2 partial agonistPartial agonistPartial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
/ D3 antagonist, with good selectivity over other receptors - TalipexoleTalipexoleTalipexole is a dopamine agonist that has been proposed as an antiparkinsonian agent. It also has α1-adrenergic and α2-adrenergic agonist activity....
- selective for D2 over other dopamine receptors, but also acts as α2-adrenoceptor agonist and 5HT3 antagonist. - PiribedilPiribedilPiribedil is an antiparkinsonian agent and piperazine derivative which acts as a D2 and D3 receptor agonist...
- also D3 receptor agonist and α2-adrenergic antagonist - LSDLSDLysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...
- in vitro, LSD was found to be a partial agonist and potentiates dopamine-mediated prolactin secretion in lactotrophs. LSD is also a 5HT2A agonist. - PramipexolePramipexolePramipexole is a non-ergoline dopamine agonist indicated for treating early-stage Parkinson's disease and restless legs syndrome...
- also D3, D4 receptor agonist - QuinpiroleQuinpiroleQuinpirole is a psychoactive drug and research chemical which acts as a selective D2 and D3 receptor agonist. It is used in scientific research. Quinpirole has been shown to increase locomotion and sniffing behavior in mice treated with it....
- also D3 receptor agonist - QuineloraneQuineloraneQuinelorane is a drug which acts as a dopamine agonist selective for the D2 subtype....
- MethylphenidateMethylphenidateMethylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
- Salvinorin ASalvinorin ASalvinorin A is the main active psychotropic molecule in Salvia divinorum, a Mexican plant which has a long history of use as an entheogen by indigenous Mazatec shamans...
- partial agonist. Also k-opioid agonist. - BromocriptineBromocriptineBromocriptine , an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease , hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.- Indications :Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly...
- RopiniroleRopiniroleRopinirole is a non-ergoline dopamine agonist. It is manufactured by GlaxoSmithKline , Cipla and Sun Pharmaceutical. It is used in the treatment of Parkinson's disease...
Antagonists
- L-741,626L-741,626L-741,626 is a drug which acts as a potent and selective antagonist for the dopamine receptor D2. It has good selectivity over the related D3 and D4 subtypes and other receptors...
(3-[4-(4-Chlorophenyl)-4-hydroxypiperidin-l-yl]methyl-1H-indole) - highly selective D2 antagonist - MelperoneMelperoneMelperone is an atypical antipsychotic of the butyrophenone chemical class.- External links :*...
- D2 antagonist but also 5HT2A antagonist - RisperidoneRisperidoneRisperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...
- D2 antagonist but also 5HT2A antagonist - ZiprasidoneZiprasidoneZiprasidone was the fifth atypical antipsychotic to gain FDA approval . In the United States, Ziprasidone is Food and Drug Administration approved for the treatment of schizophrenia, and the intramuscular injection form of ziprasidone is approved for acute agitation in schizophrenic patients...
- D2 antagonist but also 5HT2A antagonist - RacloprideRacloprideRaclopride is a synthetic compound that acts as an antagonist on D2 dopamine receptors.It can be radiolabelled with the carbon-11 radioisotope and used in positron emission tomography scanning to assess the degree of dopamine binding to the D2 Dopamine receptor.For example, one study found...
- Radiolabled C11raclopride is commonly employed in Positron emission tomography studies - ClozapineClozapineClozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...
- QuetiapineQuetiapineQuetiapine , is an atypical antipsychotic approved for the treatment of schizophrenia, and bipolar disorder....
- DomperidoneDomperidoneDomperidone is an antidopaminergic drug, developed by Janssen Pharmaceutica, and used orally, rectally or intravenously, generally to suppress nausea and vomiting, or as a prokinetic agent...
- D2 and D3 antagonist
D2Sh selective (presynaptic autoreceptors)
- AmisulprideAmisulprideAmisulpride , is an atypical antipsychotic used to treat psychosis in schizophrenia and episodes of mania in bipolar disorder. In small doses it is also used to treat depression. It was introduced by Sanofi-Aventis in the 1990s.-Pharmacology:Amisulpride functions primarily as a D2 and D3 receptor...
(low doses) - UH-232UH-232UH-232 is a drug which acts as a subtype selective mixed agonist-antagonist for dopamine receptors, acting as a weak partial agonist at the D3 subtype, and an antagonist at D2Sh autoreceptors on dopaminergic nerve terminals. This causes dopamine release in the brain and has a stimulant effect, as...
Interactions
Dopamine receptor D2 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Adenosine A2A receptor
Adenosine A2A receptor
The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, but also denotes the human gene encoding it.-Structure:This protein is a member of the G protein-coupled receptor family which possess seven transmembrane alpha helices...
, EPB41L1
EPB41L1
Band 4.1-like protein 1 is a protein that in humans is encoded by the EPB41L1 gene.-Interactions:EPB41L1 has been shown to interact with ITPR1, Dopamine receptor D2, Dopamine receptor D3, CENTG1 and Nuclear mitotic apparatus protein 1....
and PPP1R9B
PPP1R9B
Neurabin-2 is a protein that in humans is encoded by the PPP1R9B gene.-Interactions:PPP1R9B has been shown to interact with PPP1CB, PPP1CA, Dopamine receptor D2, P16, PPP1CC, T-cell lymphoma invasion and metastasis-inducing protein 1 and PPP1R2....
.