RGD Reference Report - The physiology, signaling, and pharmacology of dopamine receptors. - Rat Genome Database

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The physiology, signaling, and pharmacology of dopamine receptors.

Authors: Beaulieu, JM  Gainetdinov, RR 
Citation: Beaulieu JM and Gainetdinov RR, Pharmacol Rev. 2011 Mar;63(1):182-217. doi: 10.1124/pr.110.002642. Epub 2011 Feb 8.
RGD ID: 11041134
Pubmed: PMID:21303898   (View Abstract at PubMed)
DOI: DOI:10.1124/pr.110.002642   (Journal Full-text)

G protein-coupled dopamine receptors (D1, D2, D3, D4, and D5) mediate all of the physiological functions of the catecholaminergic neurotransmitter dopamine, ranging from voluntary movement and reward to hormonal regulation and hypertension. Pharmacological agents targeting dopaminergic neurotransmission have been clinically used in the management of several neurological and psychiatric disorders, including Parkinson's disease, schizophrenia, bipolar disorder, Huntington's disease, attention deficit hyperactivity disorder (ADHD(1)), and Tourette's syndrome. Numerous advances have occurred in understanding the general structural, biochemical, and functional properties of dopamine receptors that have led to the development of multiple pharmacologically active compounds that directly target dopamine receptors, such as antiparkinson drugs and antipsychotics. Recent progress in understanding the complex biology of dopamine receptor-related signal transduction mechanisms has revealed that, in addition to their primary action on cAMP-mediated signaling, dopamine receptors can act through diverse signaling mechanisms that involve alternative G protein coupling or through G protein-independent mechanisms via interactions with ion channels or proteins that are characteristically implicated in receptor desensitization, such as beta-arrestins. One of the future directions in managing dopamine-related pathologic conditions may involve a transition from the approaches that directly affect receptor function to a precise targeting of postreceptor intracellular signaling modalities either directly or through ligand-biased signaling pharmacology. In this comprehensive review, we discuss dopamine receptor classification, their basic structural and genetic organization, their distribution and functions in the brain and the periphery, and their regulation and signal transduction mechanisms. In addition, we discuss the abnormalities of dopamine receptor expression, function, and signaling that are documented in human disorders and the current pharmacology and emerging trends in the development of novel therapeutic agents that act at dopamine receptors and/or on related signaling events.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PPP1R1BHumandopamine signaling pathway   TAS  RGD 
PTPN5Humandopamine signaling pathway   TAS  RGD 
Ppp1r1bRatdopamine signaling pathway   ISOPPP1R1B (Homo sapiens) RGD 
Ppp1r1bMousedopamine signaling pathway   ISOPPP1R1B (Homo sapiens) RGD 
Ptpn5Ratdopamine signaling pathway   ISOPTPN5 (Homo sapiens) RGD 
Ptpn5Mousedopamine signaling pathway   ISOPTPN5 (Homo sapiens) RGD 
ARRB1Humandopamine signaling pathway via D1 family of receptors  TAS  RGD 
ARRB2Humandopamine signaling pathway via D1 family of receptors  TAS  RGD 
Arrb1Ratdopamine signaling pathway via D1 family of receptors  ISOARRB2 (Homo sapiens) RGD 
Arrb1Mousedopamine signaling pathway via D1 family of receptors  ISOARRB1 (Homo sapiens) RGD 
Arrb1Mousedopamine signaling pathway via D1 family of receptors  ISOARRB2 (Homo sapiens) RGD 
Arrb1Ratdopamine signaling pathway via D1 family of receptors  ISOARRB1 (Homo sapiens) RGD 
Arrb2Ratdopamine signaling pathway via D1 family of receptors  ISOARRB2 (Homo sapiens) RGD 
Arrb2Mousedopamine signaling pathway via D1 family of receptors  ISOARRB2 (Homo sapiens) RGD 
DRD1Humandopamine signaling pathway via D1 family of receptors  TAS  RGD 
DRD5Humandopamine signaling pathway via D1 family of receptors  TAS  RGD 
Drd1Mousedopamine signaling pathway via D1 family of receptors  ISODRD1 (Homo sapiens) RGD 
Drd1Ratdopamine signaling pathway via D1 family of receptors  ISODRD1 (Homo sapiens) RGD 
Drd5Mousedopamine signaling pathway via D1 family of receptors  ISODRD5 (Homo sapiens) RGD 
Drd5Ratdopamine signaling pathway via D1 family of receptors  ISODRD5 (Homo sapiens) RGD 
GRK2Humandopamine signaling pathway via D1 family of receptors  TAS  RGD 
GRK3Humandopamine signaling pathway via D1 family of receptors  TAS  RGD 
GRK5Humandopamine signaling pathway via D1 family of receptors  TAS  RGD 
GRK6Humandopamine signaling pathway via D1 family of receptors  TAS  RGD 
Grk2Ratdopamine signaling pathway via D1 family of receptors  ISOGRK2 (Homo sapiens) RGD 
Grk2Mousedopamine signaling pathway via D1 family of receptors  ISOGRK2 (Homo sapiens) RGD 
Grk3Ratdopamine signaling pathway via D1 family of receptors  ISOGRK3 (Homo sapiens) RGD 
Grk3Mousedopamine signaling pathway via D1 family of receptors  ISOGRK3 (Homo sapiens) RGD 
Grk5Ratdopamine signaling pathway via D1 family of receptors  ISOGRK5 (Homo sapiens) RGD 
Grk5Mousedopamine signaling pathway via D1 family of receptors  ISOGRK5 (Homo sapiens) RGD 
Grk6Ratdopamine signaling pathway via D1 family of receptors  ISOGRK6 (Homo sapiens) RGD 
Grk6Mousedopamine signaling pathway via D1 family of receptors  ISOGRK6 (Homo sapiens) RGD 
RGS2Humandopamine signaling pathway via D1 family of receptors  TAS  RGD 
RGS4Humandopamine signaling pathway via D1 family of receptors  TAS  RGD 
RGS7Humandopamine signaling pathway via D1 family of receptors  TAS  RGD 
RGS7BPHumandopamine signaling pathway via D1 family of receptors  TAS  RGD 
RGS9Humandopamine signaling pathway via D1 family of receptors  TAS  RGD 
Rgs2Mousedopamine signaling pathway via D1 family of receptors  ISORGS2 (Homo sapiens) RGD 
Rgs2Ratdopamine signaling pathway via D1 family of receptors  ISORGS2 (Homo sapiens) RGD 
Rgs4Mousedopamine signaling pathway via D1 family of receptors  ISORGS4 (Homo sapiens) RGD 
Rgs4Ratdopamine signaling pathway via D1 family of receptors  ISORGS4 (Homo sapiens) RGD 
Rgs7Mousedopamine signaling pathway via D1 family of receptors  ISORGS7 (Homo sapiens) RGD 
Rgs7Ratdopamine signaling pathway via D1 family of receptors  ISORGS7 (Homo sapiens) RGD 
Rgs7bpMousedopamine signaling pathway via D1 family of receptors  ISORGS7BP (Homo sapiens) RGD 
Rgs7bpRatdopamine signaling pathway via D1 family of receptors  ISORGS7BP (Homo sapiens) RGD 
Rgs9Ratdopamine signaling pathway via D1 family of receptors  ISORGS9 (Homo sapiens) RGD 
Rgs9Mousedopamine signaling pathway via D1 family of receptors  ISORGS9 (Homo sapiens) RGD 
ARRB1Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
ARRB2Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
Arrb1Mousedopamine signaling pathway via D2 family of receptors  ISOARRB1 (Homo sapiens) RGD 
Arrb1Mousedopamine signaling pathway via D2 family of receptors  ISOARRB2 (Homo sapiens) RGD 
Arrb1Ratdopamine signaling pathway via D2 family of receptors  ISOARRB1 (Homo sapiens) RGD 
Arrb1Ratdopamine signaling pathway via D2 family of receptors  ISOARRB2 (Homo sapiens) RGD 
Arrb2Mousedopamine signaling pathway via D2 family of receptors  ISOARRB2 (Homo sapiens) RGD 
Arrb2Ratdopamine signaling pathway via D2 family of receptors  ISOARRB2 (Homo sapiens) RGD 
DRD2Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
DRD3Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
DRD4Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
Drd2Mousedopamine signaling pathway via D2 family of receptors  ISODRD2 (Homo sapiens) RGD 
Drd2Ratdopamine signaling pathway via D2 family of receptors  ISODRD2 (Homo sapiens) RGD 
Drd3Mousedopamine signaling pathway via D2 family of receptors  ISODRD3 (Homo sapiens) RGD 
Drd3Ratdopamine signaling pathway via D2 family of receptors  ISODRD3 (Homo sapiens) RGD 
Drd4Mousedopamine signaling pathway via D2 family of receptors  ISODRD4 (Homo sapiens) RGD 
Drd4Ratdopamine signaling pathway via D2 family of receptors  ISODRD4 (Homo sapiens) RGD 
GRK2Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
GRK3Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
GRK5Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
GRK6Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
Grk2Mousedopamine signaling pathway via D2 family of receptors  ISOGRK2 (Homo sapiens) RGD 
Grk2Ratdopamine signaling pathway via D2 family of receptors  ISOGRK2 (Homo sapiens) RGD 
Grk3Mousedopamine signaling pathway via D2 family of receptors  ISOGRK3 (Homo sapiens) RGD 
Grk3Ratdopamine signaling pathway via D2 family of receptors  ISOGRK3 (Homo sapiens) RGD 
Grk5Mousedopamine signaling pathway via D2 family of receptors  ISOGRK5 (Homo sapiens) RGD 
Grk5Ratdopamine signaling pathway via D2 family of receptors  ISOGRK5 (Homo sapiens) RGD 
Grk6Mousedopamine signaling pathway via D2 family of receptors  ISOGRK6 (Homo sapiens) RGD 
Grk6Ratdopamine signaling pathway via D2 family of receptors  ISOGRK6 (Homo sapiens) RGD 
RGS2Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
RGS4Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
RGS7Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
RGS7BPHumandopamine signaling pathway via D2 family of receptors  TAS  RGD 
RGS9Humandopamine signaling pathway via D2 family of receptors  TAS  RGD 
Rgs2Mousedopamine signaling pathway via D2 family of receptors  ISORGS2 (Homo sapiens) RGD 
Rgs2Ratdopamine signaling pathway via D2 family of receptors  ISORGS2 (Homo sapiens) RGD 
Rgs4Mousedopamine signaling pathway via D2 family of receptors  ISORGS4 (Homo sapiens) RGD 
Rgs4Ratdopamine signaling pathway via D2 family of receptors  ISORGS4 (Homo sapiens) RGD 
Rgs7Mousedopamine signaling pathway via D2 family of receptors  ISORGS7 (Homo sapiens) RGD 
Rgs7Ratdopamine signaling pathway via D2 family of receptors  ISORGS7 (Homo sapiens) RGD 
Rgs7bpMousedopamine signaling pathway via D2 family of receptors  ISORGS7BP (Homo sapiens) RGD 
Rgs7bpRatdopamine signaling pathway via D2 family of receptors  ISORGS7BP (Homo sapiens) RGD 
Rgs9Ratdopamine signaling pathway via D2 family of receptors  ISORGS9 (Homo sapiens) RGD 
Rgs9Mousedopamine signaling pathway via D2 family of receptors  ISORGS9 (Homo sapiens) RGD 
DRD2HumanG protein mediated signaling pathway via Galphai family  TAS  RGD 
DRD3HumanG protein mediated signaling pathway via Galphai family  TAS  RGD 
DRD4HumanG protein mediated signaling pathway via Galphai family  TAS  RGD 
Drd2RatG protein mediated signaling pathway via Galphai family  ISODRD2 (Homo sapiens) RGD 
Drd2MouseG protein mediated signaling pathway via Galphai family  ISODRD2 (Homo sapiens) RGD 
Drd3RatG protein mediated signaling pathway via Galphai family  ISODRD2 (Homo sapiens) RGD 
Drd3MouseG protein mediated signaling pathway via Galphai family  ISODRD2 (Homo sapiens) RGD 
Drd4RatG protein mediated signaling pathway via Galphai family  ISODRD4 (Homo sapiens) RGD 
Drd4MouseG protein mediated signaling pathway via Galphai family  ISODRD4 (Homo sapiens) RGD 
RGS2HumanG protein mediated signaling pathway via Galphai family  TAS  RGD 
RGS4HumanG protein mediated signaling pathway via Galphai family  TAS  RGD 
RGS7HumanG protein mediated signaling pathway via Galphai family  TAS  RGD 
RGS7BPHumanG protein mediated signaling pathway via Galphai family  TAS  RGD 
RGS9HumanG protein mediated signaling pathway via Galphai family  TAS  RGD 
Rgs2MouseG protein mediated signaling pathway via Galphai family  ISORGS2 (Homo sapiens) RGD 
Rgs2RatG protein mediated signaling pathway via Galphai family  ISORGS2 (Homo sapiens) RGD 
Rgs4MouseG protein mediated signaling pathway via Galphai family  ISORGS4 (Homo sapiens) RGD 
Rgs4RatG protein mediated signaling pathway via Galphai family  ISORGS4 (Homo sapiens) RGD 
Rgs7MouseG protein mediated signaling pathway via Galphai family  ISORGS7 (Homo sapiens) RGD 
Rgs7RatG protein mediated signaling pathway via Galphai family  ISORGS7 (Homo sapiens) RGD 
Rgs7bpMouseG protein mediated signaling pathway via Galphai family  ISORGS7BP (Homo sapiens) RGD 
Rgs7bpRatG protein mediated signaling pathway via Galphai family  ISORGS7BP (Homo sapiens) RGD 
Rgs9RatG protein mediated signaling pathway via Galphai family  ISORGS9 (Homo sapiens) RGD 
Rgs9MouseG protein mediated signaling pathway via Galphai family  ISORGS9 (Homo sapiens) RGD 
DRD1HumanG protein mediated signaling pathway via Galphas family  TAS  RGD 
DRD5HumanG protein mediated signaling pathway via Galphas family  TAS  RGD 
Drd1RatG protein mediated signaling pathway via Galphas family  ISODRD1 (Homo sapiens) RGD 
Drd1MouseG protein mediated signaling pathway via Galphas family  ISODRD1 (Homo sapiens) RGD 
Drd5RatG protein mediated signaling pathway via Galphas family  ISODRD5 (Homo sapiens) RGD 
Drd5MouseG protein mediated signaling pathway via Galphas family  ISODRD5 (Homo sapiens) RGD 
RGS2HumanG protein mediated signaling pathway via Galphas family  TAS  RGD 
RGS4HumanG protein mediated signaling pathway via Galphas family  TAS  RGD 
RGS7HumanG protein mediated signaling pathway via Galphas family  TAS  RGD 
RGS7BPHumanG protein mediated signaling pathway via Galphas family  TAS  RGD 
RGS9HumanG protein mediated signaling pathway via Galphas family  TAS  RGD 
Rgs2RatG protein mediated signaling pathway via Galphas family  ISORGS2 (Homo sapiens) RGD 
Rgs2MouseG protein mediated signaling pathway via Galphas family  ISORGS2 (Homo sapiens) RGD 
Rgs4RatG protein mediated signaling pathway via Galphas family  ISORGS4 (Homo sapiens) RGD 
Rgs4MouseG protein mediated signaling pathway via Galphas family  ISORGS4 (Homo sapiens) RGD 
Rgs7RatG protein mediated signaling pathway via Galphas family  ISORGS7 (Homo sapiens) RGD 
Rgs7MouseG protein mediated signaling pathway via Galphas family  ISORGS7 (Homo sapiens) RGD 
Rgs7bpRatG protein mediated signaling pathway via Galphas family  ISORGS7BP (Homo sapiens) RGD 
Rgs7bpMouseG protein mediated signaling pathway via Galphas family  ISORGS7BP (Homo sapiens) RGD 
Rgs9RatG protein mediated signaling pathway via Galphas family  ISORGS9 (Homo sapiens) RGD 
Rgs9MouseG protein mediated signaling pathway via Galphas family  ISORGS9 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Arrb1  (arrestin, beta 1)
Arrb2  (arrestin, beta 2)
Drd1  (dopamine receptor D1)
Drd2  (dopamine receptor D2)
Drd3  (dopamine receptor D3)
Drd4  (dopamine receptor D4)
Drd5  (dopamine receptor D5)
Grk2  (G protein-coupled receptor kinase 2)
Grk3  (G protein-coupled receptor kinase 3)
Grk5  (G protein-coupled receptor kinase 5)
Grk6  (G protein-coupled receptor kinase 6)
Ppp1r1b  (protein phosphatase 1, regulatory (inhibitor) subunit 1B)
Ptpn5  (protein tyrosine phosphatase, non-receptor type 5)
Rgs2  (regulator of G-protein signaling 2)
Rgs4  (regulator of G-protein signaling 4)
Rgs7  (regulator of G-protein signaling 7)
Rgs7bp  (regulator of G-protein signaling 7 binding protein)
Rgs9  (regulator of G-protein signaling 9)

Genes (Mus musculus)
Arrb1  (arrestin, beta 1)
Arrb2  (arrestin, beta 2)
Drd1  (dopamine receptor D1)
Drd2  (dopamine receptor D2)
Drd3  (dopamine receptor D3)
Drd4  (dopamine receptor D4)
Drd5  (dopamine receptor D5)
Grk2  (G protein-coupled receptor kinase 2)
Grk3  (G protein-coupled receptor kinase 3)
Grk5  (G protein-coupled receptor kinase 5)
Grk6  (G protein-coupled receptor kinase 6)
Ppp1r1b  (protein phosphatase 1, regulatory inhibitor subunit 1B)
Ptpn5  (protein tyrosine phosphatase, non-receptor type 5)
Rgs2  (regulator of G-protein signaling 2)
Rgs4  (regulator of G-protein signaling 4)
Rgs7  (regulator of G protein signaling 7)
Rgs7bp  (regulator of G-protein signalling 7 binding protein)
Rgs9  (regulator of G-protein signaling 9)

Genes (Homo sapiens)
ARRB1  (arrestin beta 1)
ARRB2  (arrestin beta 2)
DRD1  (dopamine receptor D1)
DRD2  (dopamine receptor D2)
DRD3  (dopamine receptor D3)
DRD4  (dopamine receptor D4)
DRD5  (dopamine receptor D5)
GRK2  (G protein-coupled receptor kinase 2)
GRK3  (G protein-coupled receptor kinase 3)
GRK5  (G protein-coupled receptor kinase 5)
GRK6  (G protein-coupled receptor kinase 6)
PPP1R1B  (protein phosphatase 1 regulatory inhibitor subunit 1B)
PTPN5  (protein tyrosine phosphatase non-receptor type 5)
RGS2  (regulator of G protein signaling 2)
RGS4  (regulator of G protein signaling 4)
RGS7  (regulator of G protein signaling 7)
RGS7BP  (regulator of G protein signaling 7 binding protein)
RGS9  (regulator of G protein signaling 9)


Additional Information