Nomenclature: D5 receptor

Family: Dopamine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 477 4p16.1 DRD5 dopamine receptor D5 20
Mouse 7 478 5 B3 Drd5 dopamine receptor D5 21
Rat 7 475 14q21 Drd5 dopamine receptor D5 22
Previous and Unofficial Names
D1B
D1B
DRD1L2
DRD1B
D(1B) dopamine receptor
Dopamine receptor D5
d(5) dopamine receptor
dopamine D5 receptor
dopamine receptor 5
Drd-5
Gpcr1
D5R
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
dopamine
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
lisuride Hs Partial agonist 8.5 pKi 12
pKi 8.5 [12]
(+)-SKF-82526 Hs Full agonist 7.8 pKi 20
pKi 7.8 [20]
cabergoline Hs Full agonist 7.7 pKi 12
pKi 7.7 [12]
apomorphine Hs Partial agonist 6.4 – 7.8 pKi 12,20
pKi 6.4 – 7.8 [12,20]
SKF-38393 Hs Full agonist 7.0 pKi 20
pKi 7.0 [20]
beta-ergocriptine Hs Full agonist 6.9 pKi 20
pKi 6.9 [20]
pergolide Hs Full agonist 6.0 – 7.5 pKi 12,20
pKi 6.0 – 7.5 [12,20]
dopamine Hs Full agonist 6.6 pKi 20
pKi 6.6 [20]
SKF-76783 Hs Full agonist 6.3 pKi 20
pKi 6.3 [20]
bromocriptine Hs Full agonist 6.3 pKi 12,20
pKi 6.3 [12,20]
(-)-SKF-82526 Hs Full agonist 6.1 pKi 20
pKi 6.1 [20]
(+)-ADTN Hs Full agonist 6.0 pKi 20
pKi 6.0 [20]
rotigotine Hs Full agonist 6.0 pKi 20
pKi 6.0 [20]
NPA Hs Full agonist 5.9 pKi 20
pKi 5.9 [20]
5-HT Hs Full agonist 5.5 pKi 20
pKi 5.5 [20]
noradrenaline Hs Full agonist 4.9 pKi 20
pKi 4.9 [20]
A68930 Hs Agonist 6.6 pEC50 14
pEC50 6.6 (EC50 2.514x10-7 M) [14]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]SCH-23390 Hs Antagonist 9.2 pKd 17
pKd 9.2 (Kd 5.8x10-10 M) [17]
SKF-83556 Hs Antagonist 9.4 pKi 20
pKi 9.4 [20]
SCH-23390 Hs Antagonist 7.5 – 9.5 pKi 20
pKi 7.5 – 9.5 [20]
ecopipam Hs Antagonist 8.3 pKi 20
pKi 8.3 [20]
cis-flupentixol Hs Antagonist 8.1 pKi 20
pKi 8.1 [20]
fluphenazine Hs Antagonist 7.9 pKi 20
pKi 7.9 [20]
(+)-butaclamol Hs Antagonist 7.6 pKi 20
pKi 7.6 [20]
chlorpromazine Hs Antagonist 6.9 pKi 20
pKi 6.9 [20]
clozapine Hs Antagonist 6.6 pKi 20
pKi 6.6 [20]
haloperidol Hs Antagonist 6.3 pKi 20
pKi 6.3 [20]
ketanserin Hs Antagonist 5.6 pKi 20
pKi 5.6 [20]
thioridazine Hs Antagonist 5.6 pKi 20
pKi 5.6 [20]
spiperone Hs Antagonist 5.3 pKi 20
pKi 5.3 [20]
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  20,22-23
Tissue Distribution
Pulmonary artery.
Species:  Human
Technique:  Western Blot and Immunohistochemistry.
References:  18
Brain: striatum, hippocampus, dentate gyrus, subiculum, frontal cortex, limbic cortex, occipital cortex, cerebellum.
Species:  Human
Technique:  Western Blot and Immunocytochemistry.
References:  9
Forebrain, diencephalon.
Species:  Rat
Technique:  Immunohistochemistry.
References:  2
Brain: substantia nigra, inferior colliculus, oculomotor nucleus, superior colliculus, hypothalamus, mammillary nucleus, supraoptic nucleus, thalamus, striatum, hippocampus, dentate gyrus, subiculum, frontal cortex, limbic cortex, occipital cortex, cerebellum, olfactory bulb.
Species:  Rat
Technique:  Western Blot and Immunocytochemistry.
References:  9
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays
Measurement of cAMP levels in CHO cells transfected with the human D5 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Stimulation of cAMP accumulation.
References:  6,15
Measurement of IP levels in GH4C1 cells transfected with the human D5 receptor.
Species:  Human
Tissue:  GH4C1 cells.
Response measured:  Inhibition of IP accumulation.
References:  24
Measurement of cAMP levels in HEK 293 cells transfected with the human D5 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  27
Physiological Functions
Potentiation of burst firing in subthalamic nucleus through modulation of L-type Ca2+ conductance.
Species:  Rat
Tissue:  Brain.
References:  1
Modulation of hippocampal acetylcholine release.
Species:  Rat
Tissue:  In vivo.
References:  5
Activation of D5 receptors enhances GABAA currents in striatal cholinergic neurones.
Species:  Rat
Tissue:  Brain.
References:  25
Blockade of D5 receptors prevents long-term depression in corticostriatal neurones.
Species:  Mouse
Tissue:  Brain.
References:  3
Enhancement of NMDA receptor-mediated current in the ventral tegmental area.
Species:  Rat
Tissue:  Brain.
References:  19
Physiological Consequences of Altering Gene Expression
D5 receptor knockout mice exhibit increased heart weight.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  7
D5 receptor knockout mice display hypertension.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  7,26-28
D5 knockout mice display altered exploratory locomotion, startle and prepulse inhibition.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  8
D5 receptor knockout mice exhibit reduced acetylcholine release in the hippocampus.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  10
D5 receptor knockout mice exhibit increased phospholipase D activity in the kidney.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  26
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Drd5tm1Sib Drd5tm1Sib/Drd5tm1Sib
involves: 129S4/SvJae * C57BL/6
MGI:94927  MP:0002909 abnormal adrenal gland physiology PMID: 12486173 
Drd5tm1Sib Drd5tm1Sib/Drd5tm1Sib
involves: 129S4/SvJae * C57BL/6
MGI:94927  MP:0002136 abnormal kidney physiology PMID: 15598876 
Drd5tm1Sib Drd5tm1Sib/Drd5tm1Sib
B6.129S4-Drd5
MGI:94927  MP:0002136 abnormal kidney physiology PMID: 15598876 
Drd5tm1Sib Drd5tm1Sib/Drd5tm1Sib
involves: 129S4/SvJae * C57BL/6
MGI:94927  MP:0004183 abnormal sympathetic nervous system physiology PMID: 12486173 
Drd5tm1Sib Drd5tm1Sib/Drd5tm1Sib
involves: 129S4/SvJae * C57BL/6
MGI:94927  MP:0000231 hypertension PMID: 12486173 
Drd5tm1Sib Drd5tm1Sib/Drd5tm1Sib
involves: 129S4/SvJae * C57BL/6
MGI:94927  MP:0002833 increased heart weight PMID: 12486173 
Drd5tm1Sib Drd5tm1Sib/Drd5tm1Sib
involves: 129S4/SvJae * C57BL/6
MGI:94927  MP:0002842 increased systemic arterial blood pressure PMID: 12486173  15598876 
Drd5tm1Sib Drd5tm1Sib/Drd5tm1Sib
B6.129S4-Drd5
MGI:94927  MP:0002842 increased systemic arterial blood pressure PMID: 15598876 
Drd5tm1Sib Drd5tm1Sib/Drd5tm1Sib
involves: 129S4/SvJae * C57BL/6
MGI:94927  MP:0006143 increased systemic arterial diastolic blood pressure PMID: 12486173  15598876 
Drd5tm1Sib Drd5tm1Sib/Drd5tm1Sib
B6.129S4-Drd5
MGI:94927  MP:0006143 increased systemic arterial diastolic blood pressure PMID: 15598876 
Drd5tm1Sib Drd5tm1Sib/Drd5tm1Sib
involves: 129S4/SvJae * C57BL/6
MGI:94927  MP:0006144 increased systemic arterial systolic blood pressure PMID: 12486173  15598876 
Drd5tm1Sib Drd5tm1Sib/Drd5tm1Sib
B6.129S4-Drd5
MGI:94927  MP:0006144 increased systemic arterial systolic blood pressure PMID: 15598876 
Drd5tm1Dgen Drd5tm1Dgen/Drd5tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:94927  MP:0002169 no abnormal phenotype detected
Clinically-Relevant Mutations and Pathophysiology
Disease:  Cervical dystonia
OMIM:  126453
Orphanet:  93962
Comments: 
References:  16
Mutations not determined
Disease:  Benign essential blepharospasm
OMIM:  606798
Orphanet:  93955
Comments: 
References:  13
Mutations not determined
Biologically Significant Variants
Type:  Repeat polymorphism.
Species:  Human
Description:  Microsatellite polymorphism may increase risk of ADHD.
References:  11
General Comments
Intronless in the coding sequence. Two pseudogenes have been identified[4].
Available Assays
DiscoveRx PathHunter® CHO-K1 DRD5 β-Arrestin Cell Line (Cat no. 93-0426C2)
PathHunter® eXpress DRD5 CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0426E2CP0M)
more info

REFERENCES

1. Baufreton J, Garret M, Rivera A, de la Calle A, Gonon F, Dufy B, Bioulac B, Taupignon A. (2003) D5 (not D1) dopamine receptors potentiate burst-firing in neurons of the subthalamic nucleus by modulating an L-type calcium conductance. J Neurosci23: 816-825. [PMID:12574410]

2. Berlanga ML, Simpson TK, Alcantara AA. (2005) Dopamine D5 receptor localization on cholinergic neurons of the rat forebrain and diencephalon: a potential neuroanatomical substrate involved in mediating dopaminergic influences on acetylcholine release. J Comp Neurol492: 34-49. [PMID:16175554]

3. Centonze D, Grande C, Saulle E, Martin AB, Gubellini P, Pavón N, Pisani A, Bernardi G, Moratalla R, Calabresi P. (2003) Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity. J Neurosci23: 8506-8512. [PMID:13679419]

4. Grandy DK, Zhang YA, Bouvier C, Zhou QY, Johnson RA, Allen L, Buck K, Bunzow JR, Salon J, Civelli O. (1991) Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes. Proc. Natl. Acad. Sci. U.S.A.88: 9175-9179. [PMID:1833775]

5. Hersi AI, Kitaichi K, Srivastava LK, Gaudreau P, Quirion R. (2000) Dopamine D-5 receptor modulates hippocampal acetylcholine release. Brain Res Mol Brain Res76: 336-340. [PMID:10762709]

6. Himmler A, Stratowa C, Czernilofsky AP. (1993) Functional testing of human dopamine D1 and D5 receptors expressed in stable cAMP-responsive luciferase reporter cell lines. J Recept Res13: 79-94. [PMID:8383768]

7. Hollon TR, Bek MJ, Lachowicz JE, Ariano MA, Mezey E, Ramachandran R, Wersinger SR, Soares-da-Silva P, Liu ZF, Grinberg A, Drago J, Young WS, Westphal H, Jose PA, Sibley DR. (2002) Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive. J Neurosci22: 10801-10810. [PMID:12486173]

8. Holmes A, Hollon TR, Gleason TC, Liu Z, Dreiling J, Sibley DR, Crawley JN. (2001) Behavioral characterization of dopamine D5 receptor null mutant mice. Behav Neurosci115: 1129-1144. [PMID:11584926]

9. Khan ZU, Gutierrez A, Martin R, Penafiel A, Rivera A, de la Calle A. (2000) Dopamine D5 receptors of rat and human brain. Neuroscience100: 689-699. [PMID:11036203]

10. Laplante F, Sibley DR, Quirion R. (2004) Reduction in acetylcholine release in the hippocampus of dopamine D5 receptor-deficient mice. Neuropsychopharmacology29: 1620-1627. [PMID:15100705]

11. Manor I, Corbex M, Eisenberg J, Gritsenkso I, Bachner-Melman R, Tyano S, Ebstein RP. (2004) Association of the dopamine D5 receptor with attention deficit hyperactivity disorder (ADHD) and scores on a continuous performance test (TOVA). Am J Med Genet B Neuropsychiatr Genet127: 73-77. [PMID:15108184]

12. Millan MJ, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A. (2002) Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther303: 791-804. [PMID:12388666]

13. Misbahuddin A, Placzek MR, Chaudhuri KR, Wood NW, Bhatia KP, Warner TT. (2002) A polymorphism in the dopamine receptor DRD5 is associated with blepharospasm. Neurology58: 124-126. [PMID:11781417]

14. Nergårdh R, Oerther S, Fredholm BB. (2005) Differences between A 68930 and SKF 82958 could suggest synergistic roles of D1 and D5 receptors. Pharmacol. Biochem. Behav.82 (3): 495-505. [PMID:16318870]

15. Pedersen UB, Norby B, Jensen AA, Schiødt M, Hansen A, Suhr-Jessen P, Scheideler M, Thastrup O, Andersen PH. (1994) Characteristics of stably expressed human D1a and D1b receptors: atypical behavior of the dopamine D1b receptor. Eur. J. Pharmacol.267: 85-93. [PMID:8206133]

16. Placzek MR, Misbahuddin A, Chaudhuri KR, Wood NW, Bhatia KP, Warner TT. (2001) Cervical dystonia is associated with a polymorphism in the dopamine (D5) receptor gene. J Neurol Neurosurg Psychiatry71: 262-264. [PMID:11459908]

17. Ricci A, Amenta F. (1994) Dopamine D5 receptors in human peripheral blood lymphocytes: a radioligand binding study. J. Neuroimmunol.53 (1): 1-7. [PMID:8051291]

18. Ricci A, Mignini F, Tomassoni D, Amenta F. (2006) Dopamine receptor subtypes in the human pulmonary arterial tree. Auton Autacoid Pharmacol26: 361-369. [PMID:16968475]

19. Schilström B, Yaka R, Argilli E, Suvarna N, Schumann J, Chen BT, Carman M, Singh V, Mailliard WS, Ron D, Bonci A. (2006) Cocaine enhances NMDA receptor-mediated currents in ventral tegmental area cells via dopamine D5 receptor-dependent redistribution of NMDA receptors. J Neurosci26: 8549-8558. [PMID:16914681]

20. Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB. (1991) Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature350: 614-619. [PMID:1826762]

21. Tarantino LM, Feiner L, Alavizadeh A, Wiltshire T, Hurle B, Ornitz DM, Webber AL, Raper J, Lengeling A, Rowe LB, Bucan M. (2000) A high-resolution radiation hybrid map of the proximal portion of mouse chromosome 5. Genomics66: 55-64. [PMID:10843805]

22. Tiberi M, Jarvie KR, Silvia C, Falardeau P, Gingrich JA, Godinot N, Bertrand L, Yang-Feng TL, Fremeau RT Jr, Caron MG. (1991) Cloning, molecular characterization, and chromosomal assignment of a gene encoding a second D1 dopamine receptor subtype: differential expression pattern in rat brain compared with the D1A receptor. Proc. Natl. Acad. Sci. U.S.A.88: 7491-7495. [PMID:1831904]

23. Weinshank RL, Adham N, Macchi M, Olsen MA, Branchek TA, Hartig PR. (1991) Molecular cloning and characterization of a high affinity dopamine receptor (D1 beta) and its pseudogene. J Biol Chem266: 22427-22435. [PMID:1834671]

24. White BH, Kimura K, Sidhu A. (1999) Inhibition of hormonally induced inositol trisphosphate production in Transfected GH4C1 cells: A novel role for the D5 subtype of the dopamine receptor. Neuroendocrinology69: 209-216. [PMID:10087453]

25. Yan Z, Surmeier DJ. (1997) D5 dopamine receptors enhance Zn2+-sensitive GABA(A) currents in striatal cholinergic interneurons through a PKA/PP1 cascade. Neuron19: 1115-1126. [PMID:9390524]

26. Yang Z, Asico LD, Yu P, Wang Z, Jones JE, Bai RK, Sibley DR, Felder RA, Jose PA. (2005) D5 dopamine receptor regulation of phospholipase D. Am J Physiol Heart Circ Physiol288: H55-H61. [PMID:15598876]

27. Yang Z, Asico LD, Yu P, Wang Z, Jones JE, Escano CS, Wang X, Quinn MT, Sibley DR, Romero GG, Felder RA, Jose PA. (2006) D5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure. Am J Physiol Regul Integr Comp Physiol290: R96-R104. [PMID:16352863]

28. Yang Z, Sibley DR, Jose PA. (2004) D5 dopamine receptor knockout mice and hypertension. J Recept Signal Transduct Res24: 149-164. [PMID:15521360]

To cite this database page, please use the following:

Arvid Carlsson, Marc G. Caron, Olivier Civelli, John W. Kebabian, Saloman Z. Langer, Bernard Scatton, Jean-Charles Schwartz, Goran Sedvall, Philip Seeman, Pierre Sokoloff, Pierre F. Spano, Hubert H. M. Van Tol.
Dopamine receptors: D5 receptor. Last modified on 30/04/2014. Accessed on 01/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=218.

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