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D5 receptor

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Target not currently curated in GtoImmuPdb

Target id: 218

Nomenclature: D5 receptor

Family: Dopamine receptors

Contents:

Gene and Protein Information Click here for help
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 22
Mouse 7 478 5 20.4 cM Drd5 dopamine receptor D5 23
Rat 7 475 14q21 Drd5 dopamine receptor D5 24
Previous and Unofficial Names Click here for help
DRD1B | DRD1L2 | D(1B) dopamine receptor | dopamine receptor 5 | Gpcr1
Database Links Click here for help
Specialist databases
GPCRdb drd5_human (Hs), drd5_mouse (Mm), drd5_rat (Rn)
Other databases
Alphafold P21918 (Hs), Q8BLD9 (Mm), P25115 (Rn)
ChEMBL Target CHEMBL1850 (Hs), CHEMBL2737 (Mm), CHEMBL2281 (Rn)
DrugBank Target P21918 (Hs)
Ensembl Gene ENSG00000169676 (Hs), ENSMUSG00000039358 (Mm), ENSRNOG00000005338 (Rn)
Entrez Gene 1816 (Hs), 13492 (Mm), 25195 (Rn)
Human Protein Atlas ENSG00000169676 (Hs)
KEGG Gene hsa:1816 (Hs), mmu:13492 (Mm), rno:25195 (Rn)
OMIM 126453 (Hs)
Orphanet ORPHA121181 (Hs)
Pharos P21918 (Hs)
RefSeq Nucleotide NM_000798 (Hs), NM_013503 (Mm), NM_012768 (Rn)
RefSeq Protein NP_000789 (Hs), NP_038531 (Mm), NP_036900 (Rn)
UniProtKB P21918 (Hs), Q8BLD9 (Mm), P25115 (Rn)
Wikipedia DRD5 (Hs)
Natural/Endogenous Ligands Click here for help
dopamine
5-hydroxytryptamine
noradrenaline

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
lisuride Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 8.5 pKi 14
⤷ pKi 8.5 [14]
(+)-SKF-82526 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.8 pKi 22
⤷ pKi 7.8 [22]
cabergoline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.7 pKi 14
⤷ pKi 7.7 [14]
apomorphine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 6.4 – 7.8 pKi 14,22
⤷ pKi 6.4 – 7.8 [14,22]
SKF-38393 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 7.0 pKi 22
⤷ pKi 7.0 [22]
beta-ergocriptine Small molecule or natural product Hs Full agonist 6.9 pKi 22
⤷ pKi 6.9 [22]
pergolide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 6.0 – 7.5 pKi 14,22
⤷ pKi 6.0 – 7.5 [14,22]
dopamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 6.6 pKi 22
⤷ pKi 6.6 [22]
bromocriptine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.3 pKi 14,22
⤷ pKi 6.3 [14,22]
SKF-76783 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.3 pKi 22
⤷ pKi 6.3 [22]
(-)-SKF-82526 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.1 pKi 22
⤷ pKi 6.1 [22]
(+)-ADTN Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.0 pKi 22
⤷ pKi 6.0 [22]
rotigotine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.0 pKi 22
⤷ pKi 6.0 [22]
N-propylnorapomorphine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.9 pKi 22
⤷ pKi 5.9 [22]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 5.5 pKi 22
⤷ pKi 5.5 [22]
noradrenaline Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 4.9 pKi 22
⤷ pKi 4.9 [22]
A68930 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.6 pEC50 16
⤷ pEC50 6.6 (EC50 2.514x10-7 M) [16]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]SCH-23390 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 9.2 pKd 19
⤷ pKd 9.2 (Kd 5.8x10-10 M) [19]
SKF-83566 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.4 pKi 22
⤷ pKi 9.4 [22]
SCH-23390 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 – 9.5 pKi 22
⤷ pKi 7.5 – 9.5 [22]
ecopipam Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 pKi 22
⤷ pKi 8.3 [22]
flupentixol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.1 pKi 22
⤷ pKi 8.1 [22]
fluphenazine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.9 pKi 22
⤷ pKi 7.9 [22]
(+)-butaclamol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.6 pKi 22
⤷ pKi 7.6 [22]
chlorpromazine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.9 pKi 22
⤷ pKi 6.9 [22]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.6 pKi 22
⤷ pKi 6.6 [22]
haloperidol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.3 pKi 22
⤷ pKi 6.3 [22]
ketanserin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.6 pKi 22
⤷ pKi 5.6 [22]
thioridazine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 5.6 pKi 22
⤷ pKi 5.6 [22]
spiperone Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.3 pKi 22
⤷ pKi 5.3 [22]
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
References:  22,24-25
Tissue Distribution Click here for help
Pulmonary artery.
Species:  Human
Technique:  Western Blot and Immunohistochemistry.
References:  20
Brain: striatum, hippocampus, dentate gyrus, subiculum, frontal cortex, limbic cortex, occipital cortex, cerebellum.
Species:  Human
Technique:  Western Blot and Immunocytochemistry.
References:  10
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:  10
Cerebral cortex, basal ganglia, basal forebrain, hippocampus, diencephalon, brainstem, cerebellum, olfactory bulb, islands of Calleja, superior colliculus
Species:  Rat
Technique:  Immunohistochemistry
References:  4
Cerebral cortex, basal ganglia, basal forebrain, hippocampus, diencephalon, brainstem, cerebellum, olfactory bulb, islands of Calleja, superior colliculus
Species:  Monkey
Technique:  Immunohistochemistry
References:  4
Expression Datasets Click here for help

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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]

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Functional Assays Click here for help
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:  7,17
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:  26
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:  29
Measurement of β-arrestin recruitment in CHO cells transfected with the human D5 receptor.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  Recruitment of β-arrestin.
References:  13
Physiological Functions Click here for help
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:  21
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:  6
Activation of D5 receptors enhances GABAA currents in striatal cholinergic neurones.
Species:  Rat
Tissue:  Brain.
References:  27
Physiological Consequences of Altering Gene Expression Click here for help
D5 receptor knockout mice exhibit reduced acetylcholine release in the hippocampus.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  11
D5 receptor knockout mice exhibit increased heart weight.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  8
D5 receptor knockout mice display hypertension.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  8,28-30
D5 knockout mice display altered exploratory locomotion, startle and prepulse inhibition.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  9
D5 receptor knockout mice exhibit increased phospholipase D activity in the kidney.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  28
Phenotypes, Alleles and Disease Models Click here for help 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 Click here for help
Disease:  Benign essential blepharospasm
Synonyms: Blepharospasm [Disease Ontology: DOID:529]
Disease Ontology: DOID:529
OMIM: 606798
Orphanet: ORPHA93955
Comments:  DRD5 repeat polymorphism associated with blepharospasm.
References:  15
Disease:  Cervical dystonia
Synonyms: Autosomal dominant cervical dystonia [Orphanet: ORPHA93962]
OMIM: 126453
Orphanet: ORPHA93962
Comments:  Microsatellite polymorphism may increase incidence of cervical dystonia.
References:  18
Biologically Significant Variants Click here for help
Type:  Repeat polymorphism
Species:  Human
Description:  Microsatellite polymorphism may increase risk of ADHD.
References:  12
General Comments
The gene for this receptor is intronless in the coding sequence. Two pseudogenes have been identified [5].

References

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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 Neurosci, 23 (3): 816-25. [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 Neurol, 492 (1): 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 Neurosci, 23 (24): 8506-12. [PMID:13679419]

4. Ciliax BJ, Nash N, Heilman C, Sunahara R, Hartney A, Tiberi M, Rye DB, Caron MG, Niznik HB, Levey AI. (2000) Dopamine D(5) receptor immunolocalization in rat and monkey brain. Synapse, 37 (2): 125-45. [PMID:10881034]

5. 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 USA, 88 (20): 9175-9. [PMID:1833775]

6. Hersi AI, Kitaichi K, Srivastava LK, Gaudreau P, Quirion R. (2000) Dopamine D-5 receptor modulates hippocampal acetylcholine release. Brain Res Mol Brain Res, 76 (2): 336-40. [PMID:10762709]

7. 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 Res, 13 (1-4): 79-94. [PMID:8383768]

8. Hollon TR, Bek MJ, Lachowicz JE, Ariano MA, Mezey E, Ramachandran R, Wersinger SR, Soares-da-Silva P, Liu ZF, Grinberg A et al.. (2002) Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive. J Neurosci, 22 (24): 10801-10. [PMID:12486173]

9. 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 Neurosci, 115 (5): 1129-44. [PMID:11584926]

10. Khan ZU, Gutiérrez A, Martín R, Peñafiel A, Rivera A, de la Calle A. (2000) Dopamine D5 receptors of rat and human brain. Neuroscience, 100 (4): 689-99. [PMID:11036203]

11. Laplante F, Sibley DR, Quirion R. (2004) Reduction in acetylcholine release in the hippocampus of dopamine D5 receptor-deficient mice. Neuropsychopharmacology, 29 (9): 1620-7. [PMID:15100705]

12. 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 Genet, 127: 73-77. [PMID:15108184]

13. Meade JA, Free RB, Miller NR, Chun LS, Doyle TB, Moritz AE, Conroy JL, Watts VJ, Sibley DR. (2015) (-)-Stepholidine is a potent pan-dopamine receptor antagonist of both G protein- and β-arrestin-mediated signaling. Psychopharmacology (Berl.), 232 (5): 917-30. [PMID:25231919]

14. 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 Ther, 303 (2): 791-804. [PMID:12388666]

15. Misbahuddin A, Placzek MR, Chaudhuri KR, Wood NW, Bhatia KP, Warner TT. (2002) A polymorphism in the dopamine receptor DRD5 is associated with blepharospasm. Neurology, 58 (1): 124-6. [PMID:11781417]

16. 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]

17. 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 dopamine D1a and D1b receptors: atypical behavior of the dopamine D1b receptor. Eur J Pharmacol, 267 (1): 85-93. [PMID:8206133]

18. 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 Psychiatry, 71: 262-264. [PMID:11459908]

19. 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]

20. Ricci A, Mignini F, Tomassoni D, Amenta F. (2006) Dopamine receptor subtypes in the human pulmonary arterial tree. Auton Autacoid Pharmacol, 26 (4): 361-9. [PMID:16968475]

21. Schilström B, Yaka R, Argilli E, Suvarna N, Schumann J, Chen BT, Carman M, Singh V, Mailliard WS, Ron D et al.. (2006) Cocaine enhances NMDA receptor-mediated currents in ventral tegmental area cells via dopamine D5 receptor-dependent redistribution of NMDA receptors. J Neurosci, 26 (33): 8549-58. [PMID:16914681]

22. 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. Nature, 350 (6319): 614-9. [PMID:1826762]

23. Tarantino LM, Feiner L, Alavizadeh A, Wiltshire T, Hurle B, Ornitz DM, Webber AL, Raper J, Lengeling A, Rowe LB et al.. (2000) A high-resolution radiation hybrid map of the proximal portion of mouse chromosome 5. Genomics, 66 (1): 55-64. [PMID:10843805]

24. Tiberi M, Jarvie KR, Silvia C, Falardeau P, Gingrich JA, Godinot N, Bertrand L, Yang-Feng TL, Fremeau Jr RT, 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 USA, 88 (17): 7491-5. [PMID:1831904]

25. 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 Chem, 266 (33): 22427-35. [PMID:1834671]

26. White BH, Kimura K, Sidhu A. (1999) Inhibition of hormonally induced inositol trisphosphate production in Transfected GH4</ sup>C1 cells: A novel role for the D5 subtype of the dopamine receptor. Neuroendocrinology, 69 (3): 209-16. [PMID:10087453]

27. Yan Z, Surmeier DJ. (1997) D5 dopamine receptors enhance Zn2+-sensitive GABA(A) currents in striatal cholinergic interneurons through a PKA/PP1 cascade. Neuron, 19 (5): 1115-26. [PMID:9390524]

28. 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 Physiol, 288 (1): H55-61. [PMID:15598876]

29. Yang Z, Asico LD, Yu P, Wang Z, Jones JE, Escano CS, Wang X, Quinn MT, Sibley DR, Romero GG et al.. (2006) D5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure. Am J Physiol Regul Integr Comp Physiol, 290 (1): R96-R104. [PMID:16352863]

30. Yang Z, Sibley DR, Jose PA. (2004) D5 dopamine receptor knockout mice and hypertension. J Recept Signal Transduct Res, 24 (3): 149-64. [PMID:15521360]

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