dopamine receptor D5

D₅ receptor is a subtype of the dopamine receptor that has a 10-fold higher affinity for dopamine than the D₁ subtype. The D₅ subtype is a G-protein coupled receptor, which promotes synthesis of cAMP by adenylyl cyclase via activation of Gα_s/olf family of G proteins.{{cite journal | vauthors = Beaulieu JM, Gainetdinov RR | title = The physiology, signaling, and pharmacology of dopamine receptors | journal = Pharmacol. Rev. | volume = 63 | issue = 1 | pages = 182–217 | year = 2011 | pmid = 21303898 | doi = 10.1124/pr.110.002642 | s2cid = 2545878 }}{{Cite journal|last=Mello|first=F. G.|title=The Ontogeny of Dopamine-Dependent Increase of Adenosine 3',5'-Cyclic Monophosphate in the Chick Retina|date=October 1978|journal=Journal of Neurochemistry|language=en|volume=31|issue=4|pages=1049–1053|doi=10.1111/j.1471-4159.1978.tb00146.x|pmid=212530|s2cid=84297833|issn=0022-3042}} Both D₅ and D₁ subtypes activate adenylyl cyclase. D₁ receptors were shown to stimulate monophasic dose-dependent accumulation of cAMP in response to dopamine, and the D₅ receptors were able to stimulate biphasic accumulation of cAMP under the same conditions, suggesting that D₅ receptors may use a different system of secondary messengers than D₁ receptors.{{cite journal | vauthors = Grandy DK, Zhang YA, Bouvier C, Zhou QY, Johnson RA, Allen L, Buck K, Bunzow JR, Salon J, Civelli O | title = Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 20 | pages = 9175–9 | year = 1991 | pmid = 1833775 | pmc = 52675 | doi = 10.1073/pnas.88.20.9175| bibcode = 1991PNAS...88.9175G | doi-access = free }}

Activation of D₅ receptors is shown to promote expression of brain-derived neurotrophic factor and increase phosphorylation of protein kinase B in rat and mice prefrontal cortex neurons.{{cite journal | vauthors = Perreault ML, Jones-Tabah J, O'Dowd BF, George SR | title = A physiological role for the dopamine D5 receptor as a regulator of BDNF and Akt signalling in rodent prefrontal cortex | journal = The International Journal of Neuropsychopharmacology | volume = 16 | issue = 2 | pages = 477–83 | year = 2013 | pmid = 22827965 | pmc = 3802523 | doi = 10.1017/S1461145712000685 }}

In vitro, D₅ receptors show high constitutive activity that is independent of binding any agonists.{{cite journal | vauthors = Tiberi M, Caron MG | title = High agonist-independent activity is a distinguishing feature of the dopamine D1B receptor subtype | journal = J. Biol. Chem. | volume = 269 | issue = 45 | pages = 27925–31 | year = 1994 | doi = 10.1016/S0021-9258(18)46876-7 | pmid = 7525564 | doi-access = free }}

D₅ receptor is highly homologous to the D₁ receptor. Their amino acid sequences are 49% to 80% identical. D₅ receptor has a long C-terminus of 93 amino acids, accounting for 26% of the entire protein. In spite of the high degree of homology between D₅ and D₁ receptors, their c-terminus tails have little similarity.{{cite journal | vauthors = O'Dowd BF, Nguyen T, Ji X, George SR | title = D5 dopamine receptor carboxyl tail involved in D5-D2 heteromer formation | journal = Biochemical and Biophysical Research Communications | volume = 431 | issue = 3 | pages = 586–9 | year = 2013 | pmid = 23318175 | pmc = 3744868 | doi = 10.1016/j.bbrc.2012.12.139 }}

In humans, D₅ receptor is encoded on the chromosome 4p15.1–p15.3.{{cite journal | vauthors = Eubanks JH, Altherr M, Wagner-McPherson C, McPherson JD, Wasmuth JJ, Evans GA | title = Localization of the D5 dopamine receptor gene to human chromosome 4p15.1-p15.3, centromeric to the Huntington's disease locus | journal = Genomics | volume = 12 | issue = 3 | pages = 510–6 | year = 1992 | pmid = 1532789 | doi=10.1016/0888-7543(92)90442-u}} The gene lacks introns and encodes a product of 477 amino acids.{{cite journal | vauthors = Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB | title = Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1 | journal = Nature | volume = 350 | issue = 6319 | pages = 614–9 | year = 1991 | pmid = 1826762 | doi = 10.1038/350614a0 | bibcode = 1991Natur.350..614S | s2cid = 4373022 }} Two pseudogenes for D₅ receptor exist that share 98% sequence with each other and 95% sequence with the functional DRD5 gene. These genes contain several in-frame stop codons that prevent these genes from transcribing a functional protein.

D₅ receptor is expressed more widely in the CNS than its close structural homolog dopamine receptor D1. It is found in neurons in amygdala, frontal cortex, hippocampus, striatum, thalamus, hypothalamus, basal forebrain, cerebellum,{{cite journal | vauthors = Wu J, Xiao H, Sun H, Zou L, Zhu LQ | title = Role of dopamine receptors in ADHD: A systematic meta-analysis | journal = Molecular Neurobiology | volume = 45 | issue = 3 | pages = 605–20 | year = 2012 | pmid = 22610946 | doi = 10.1007/s12035-012-8278-5 | s2cid = 895006 }} and midbrain.{{cite journal | vauthors = Reyes S, Cottam V, Kirik D, Double KL, Halliday GM | title = Variability in neuronal expression of dopamine receptors and transporters in the substantia nigra | journal = Movement Disorders | volume = 28 | issue = 10 | pages = 1351–9 | year = 2013 | pmid = 23674405 | doi = 10.1002/mds.25493 | hdl = 1959.4/53610 | s2cid = 25057196 | url = https://unsworks.unsw.edu.au/fapi/datastream/unsworks:12305/SOURCE01?view=true | hdl-access = free }} Dopamine receptor D₅ is exclusively expressed by large aspiny neurons in neostriatum of primates, which are typically cholinergic interneurons.{{cite journal | vauthors = Bergson C, Mrzljak L, Smiley JF, Pappy M, Levenson R, Goldman-Rakic PS | title = Regional, cellular, and subcellular variations in the distribution of D1 and D5 dopamine receptors in primate brain | journal = The Journal of Neuroscience | volume = 15 | issue = 12 | pages = 7821–36 | year = 1995 | pmid = 8613722 | doi = 10.1523/JNEUROSCI.15-12-07821.1995 | doi-access = free | pmc = 6577925 }} Within a cell, D₅ receptors are found on the membrane of soma and proximal dendrites. They are also sometimes located in the neuropil in the olfactory region, superior colliculus, and cerebellum. D₅ receptor is also found in striatal astrocytes of the rat basal ganglia.{{cite journal | vauthors = Miyazaki I, Asanuma M, Diaz-Corrales FJ, Miyoshi K, Ogawa N | title = Direct evidence for expression of dopamine receptors in astrocytes from basal ganglia | journal = Brain Research | volume = 1029 | issue = 1 | pages = 120–3 | year = 2004 | pmid = 15533323 | doi = 10.1016/j.brainres.2004.09.014 | s2cid = 34954571 }}

The receptors of this subtype are also expressed on dendritic cells and T helper cells.{{cite journal | vauthors = Prado C, Bernales S, Pacheco R | title = Modulation of T-cell mediated immunity by dopamine receptor d5 | journal = Endocrine, Metabolic & Immune Disorders Drug Targets | volume = 13 | issue = 2 | pages = 184–94 | year = 2013 | pmid = 23701196 | doi=10.2174/1871530311313020007| hdl = 10533/144001 | hdl-access = free }}

D₅ receptors are expressed in kidneys and are involved in regulation of sodium excretion. They are located on proximal convoluted tubules, and their activation suppresses the activity of sodium–hydrogen antiporter and Na+/K+-ATPase, preventing reabsorption of sodium.{{cite journal | vauthors = Hussain T, Lokhandwala MF | title = Renal dopamine receptor function in hypertension | journal = Hypertension | volume = 32 | issue = 2 | pages = 187–97 | year = 1998 | pmid = 9719042 | doi=10.1161/01.hyp.32.2.187| doi-access = free }} D₅ receptors are thought to positively regulate expression of renalase. Their faulty functioning in nephrons can contribute to hypertension.

D₅ receptor participates in the synaptic processes that underlie learning and memory. These receptors participate in the formation of LTD in rodent striatum, which is opposite to the D₁ receptor involvement with the formation of LTP in the same brain region.{{cite journal | vauthors = Centonze D, Grande C, Saulle E, Martin AB, Gubellini P, Pavón N, Pisani A, Bernardi G, Moratalla R, Calabresi P | title = Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity | journal = The Journal of Neuroscience | volume = 23 | issue = 24 | pages = 8506–12 | date = September 2003 | pmid = 13679419 | doi = 10.1523/JNEUROSCI.23-24-08506.2003 | pmc = 6740372 | doi-access = free }} D₅ receptors are also associated with the consolidation of fear memories in amygdala. It has been shown that M₁-Muscarinic receptors cooperate with D₅ receptors and beta-2 adrenergic receptors to consolidate cued fear memory. It is suggested that these G protein-coupled receptors redundantly activate phospholipase C in basolateral amygdala. One effect of the activation of phospholipase C is deactivation of KCNQ channels.{{cite journal | vauthors = Young MB, Thomas SA | title = M1-muscarinic receptors promote fear memory consolidation via phospholipase C and the M-current | journal = Journal of Neuroscience | volume = 34 | issue = 5 | pages = 1570–8 | year = 2014 | pmid = 24478341 | pmc = 3905134 | doi = 10.1523/JNEUROSCI.1040-13.2014 }} Since KCNQ channels conduct M current that raises the threshold for action potential,{{cite journal | vauthors = Schroeder BC, Hechenberger M, Weinreich F, Kubisch C, Jentsch TJ | title = KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents | journal = Journal of Biological Chemistry | volume = 275 | issue = 31 | pages = 24089–95 | year = 2000 | pmid = 10816588 | doi = 10.1074/jbc.M003245200 | doi-access = free }} deactivation of these channels leads to increased neuronal excitability and enhanced memory consolidation.

D₅ receptors may be required for long-term potentiation at the synapse between medial perforant path and dentate gyrus in murine hippocampal formation.{{cite journal | vauthors = Sariñana J, Kitamura T, Künzler P, Sultzman L, Tonegawa S | title = Differential roles of the dopamine 1-class receptors, D1R and D5R, in hippocampal dependent memory | journal = Proceedings of the National Academy of Sciences | volume = 111 | issue = 22 | pages = 8245–50 | year = 2014 | pmid = 24843151 | pmc = 4050601 | doi = 10.1073/pnas.1407395111 | bibcode = 2014PNAS..111.8245S | doi-access = free }}

Polymorphisms in the DRD5 gene, which encodes dopamine receptor D₅, have been suggested to play a role in the initiation of smoking. In a study on the association of four polymorphisms of this gene with smoking, a statistical analysis suggested that there may exist a haplotype of DRD5 that is protective against initiation of smoking.{{cite journal | vauthors = Sullivan PF, Neale MC, Silverman MA, Harris-Kerr C, Myakishev MV, Wormley B, Webb BT, Ma Y, Kendler KS, Straub RE | title = An association study of DRD5 with smoking initiation and progression to nicotine dependence | journal = Am. J. Med. Genet. | volume = 105 | issue = 3 | pages = 259–65 |date=April 2001 | pmid = 11353446 | doi = 10.1002/ajmg.1301 }}

Dinucleotide repeats of DRD5 gene are associated with ADHD in humans. 136-bp allele of the gene was shown to be a protective factor against developing this disorder, and 148-bp allele of DRD5 was shown to be a risk factor for it. There exist two types of the 148-bp allele of DRD5, a long and a short one. The short dinucleotide repeat allele is associated with ADHD, but not the long one.{{cite journal | vauthors = Kim BN, Kang D, Cho SC, Park TW, Lim MH, Chung YC, Kim JW, Hwang JW, Yoo HJ, Chung US, Son JW, Yang JC, Chung SK, Lee JY, Jung YW | title = Shorter dinucleotide repeat length in the DRD5 gene is associated with attention deficit hyperactivity disorder | journal = Psychiatric Genetics | volume = 19 | issue = 1 | pages = 57 | year = 2009 | pmid = 19125111 | doi = 10.1097/YPG.0b013e328320803c }} Another allele of DRD5 that is moderately associated with ADHD susceptibility is 150 bp.{{cite journal | vauthors = Squassina A, Lanktree M, De Luca V, Jain U, Krinsky M, Kennedy JL, Muglia P | title = Investigation of the dopamine D5 receptor gene (DRD5) in adult attention deficit hyperactivity disorder | journal = Neuroscience Letters | volume = 432 | issue = 1 | pages = 50–3 | year = 2008 | pmid = 18164132 | doi = 10.1016/j.neulet.2007.12.003 | s2cid = 7548859 }}

In a rat model of ADHD, low density of D₅ was found in the hippocampal pyramidal cell somas. Deficiency in D₅ receptors may contribute to learning problems that may be associated with ADHD.{{cite journal | vauthors = Medin T, Rinholm JE, Owe SG, Sagvolden T, Gjedde A, Storm-Mathisen J, Bergersen LH | title = Low dopamine D5 receptor density in hippocampus in an animal model of attention-deficit/hyperactivity disorder (ADHD) | journal = Neuroscience | volume = 242 | pages = 11–20 | year = 2013 | pmid = 23541742 | doi = 10.1016/j.neuroscience.2013.03.036 | s2cid = 25731931 }}

D₅ receptors may be involved in burst firing of subthalamic nucleus neurons in 6-OHDA rat model of Parkinson's disease. In this animal model, blockage of D₅ receptors with flupentixol reduces burst firing and improves motor deficits. Studies show that DRD5 T978C polymorphism is not associated with the susceptibility to PD, nor with the risk of developing motor fluctuations or hallucinations in PD.{{cite journal | vauthors = Wang J, Liu ZL, Chen B | title = Dopamine D5 receptor gene polymorphism and the risk of levodopa-induced motor fluctuations in patients with Parkinson's disease | journal = Neuroscience Letters | volume = 308 | issue = 1 | pages = 21–4 | date = July 2001 | pmid = 11445276 | doi = 10.1016/S0304-3940(01)01971-1 | s2cid = 43454552 }}{{cite journal | vauthors = Wang J, Zhao C, Chen B, Liu Z | title = Polymorphisms of dopamine receptor and transporter genes and hallucinations in Parkinson's disease | journal = Neuroscience Letters | volume = 355 | issue = 3 | pages = 193–6 | date = January 2004 | pmid = 14732464 | doi = 10.1016/j.neulet.2003.11.006 | s2cid = 44740438 }}

Several polymorphisms in DRD5 genes have been associated with susceptibility to schizophrenia. The 148 bp allele of DRD5 was linked to increased risk of schizophrenia.{{cite journal | vauthors = Muir WJ, Thomson ML, McKeon P, Mynett-Johnson L, Whitton C, Evans KL, Porteous DJ, Blackwood DH | title = Markers close to the dopamine D5 receptor gene (DRD5) show significant association with schizophrenia but not bipolar disorder | journal = American Journal of Medical Genetics | volume = 105 | issue = 2 | pages = 152–8 | year = 2001 | pmid = 11304828 | doi = 10.1002/1096-8628(2001)9999:9999<::AID-AJMG1163>3.0.CO;2-2 }} Some single-nucleotide polymorphisms in this gene, including changes in rs77434921, rs1800762, rs77434921, and rs1800762, in northern Han Chinese population.{{cite journal | vauthors = Zhao Y, Ding M, Pang H, Xu XM, Wang BJ | title = Relationship between genetic polymorphisms in the DRD5 gene and paranoid schizophrenia in northern Han Chinese | journal = Genetics and Molecular Research | volume = 13 | issue = 1 | pages = 1609–18 | year = 2014 | pmid = 24668635 | doi = 10.4238/2014.March.12.13 | doi-access = free }}

D₅ receptor is believed to participate in modulation of psychostimulant-induced locomotion. Mice lacking D₅ receptors show increased motor response to administration of methamphetamine than wild type mice,{{cite journal | vauthors = Hayashizaki S, Hirai S, Ito Y, Honda Y, Arime Y, Sora I, Okado H, Kodama T, Takada M | title = Methamphetamine increases locomotion and dopamine transporter activity in dopamine d5 receptor-deficient mice | journal = PLOS ONE | volume = 8 | issue = 10 | pages = e75975 | year = 2013 | pmid = 24155877 | pmc = 3796526 | doi = 10.1371/journal.pone.0075975 | bibcode = 2013PLoSO...875975H | doi-access = free }} which suggests that these receptors have a role in controlling motor activity.

D₅ receptor may be involved in modulation of the neuronal pathways that regulate blood pressure. Mice lacking this receptor in their brains showed hypertension and elevated blood pressure, which may have been caused by increased sympathetic tone.{{cite journal | vauthors = 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 | title = Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive | journal = The Journal of Neuroscience | volume = 22 | issue = 24 | pages = 10801–10 | year = 2002 | pmid = 12486173 | doi = 10.1523/JNEUROSCI.22-24-10801.2002 | pmc = 6758465 | doi-access = free }} D₅ receptors that are expressed in kidneys are also involved in the regulation of blood pressure via modulating expression of renalase and excretion of sodium, and disturbance of these processes can contribute to hypertension as well.

D₅ receptors negatively regulate production of IFNγ by NK cells. The expression of D₅ receptors was shown to be upregulated in NK cells in response to prolonged stimulation with recombinant interleukin 2. This upregulation inhibits proliferation of the NK cells and suppresses synthesis of IFNγ. Activation of D₅ prevents p50, part of NF-κB protein complex, from repressing the transcription of miRNA 29a. Because miRNA29a targets mRNA of IFNγ, the expression of IFNγ protein is diminished.{{cite journal | vauthors = Mikulak J, Bozzo L, Roberto A, Pontarini E, Tentorio P, Hudspeth K, Lugli E, Mavilio D | title = Dopamine inhibits the effector functions of activated NK cells via the upregulation of the D5 receptor | journal = The Journal of Immunology | volume = 193 | issue = 6 | pages = 2792–800 | year = 2014 | pmid = 25127864 | doi = 10.4049/jimmunol.1401114 | doi-access = free }}

D₅ receptors are involved in activation and differentiation of T helper 17 cells. Specifically, these receptors play a role in polarization of CD4+ T-cells into the T helper 17 cells by modulating secretion of interleukin 12 and interleukin 23 in response to stimulation with LPS.{{cite journal | vauthors = Prado C, Contreras F, González H, Díaz P, Elgueta D, Barrientos M, Herrada AA, Lladser Á, Bernales S, Pacheco R | title = Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17-mediated immunity | journal = The Journal of Immunology | volume = 188 | issue = 7 | pages = 3062–70 | year = 2012 | pmid = 22379034 | doi = 10.4049/jimmunol.1103096 | doi-access = free }}

The D₁ and D₅ receptors have a high degree of structural homology and few ligands are available that can distinguish between them as yet. However, there is a number of ligands that are selective for D_1/5 over the other dopamine receptors. The recent development of a selective D₅ antagonist has allowed the action of D₁-mediated responses to be studied in the absence of a D₅ component, but no selective D₅ agonists are yet available.

D₅ receptors show higher affinity for agonists and lower affinity for antagonists than D₁ receptors.

• Dihydrexidine
• Rotigotine{{cite journal | vauthors = Wood M, Dubois V, Scheller D, Gillard M | title = Rotigotine is a potent agonist at dopamine D₁ receptors as well as at dopamine D₂ and D₃ receptors | journal = British Journal of Pharmacology | pages = 1124–35| year = 2014 | pmid = 25339241 | doi = 10.1111/bph.12988 | volume=172 | issue = 4 | pmc=4314200}}
• SKF-83,959
• Stepholidine{{cite journal | vauthors = Meade JA, Free RB, Miller NR, Chun LS, Doyle TB, Moritz AE, Conroy JL, Watts VJ, Sibley DR | title = (-)-Stepholidine is a potent pan-dopamine receptor antagonist of both G protein- and β-arrestin-mediated signaling | journal = Psychopharmacology | year = 2014 | pmid = 25231919 | doi = 10.1007/s00213-014-3726-8 | volume=232 | issue = 5 | pages=917–30 | pmc=5234683}}
• Fenoldopam

• Flupentixol{{cite journal | vauthors = Chetrit J, Taupignon A, Froux L, Morin S, Bouali-Benazzouz R, Naudet F, Kadiri N, Gross CE, Bioulac B, Benazzouz A | title = Inhibiting subthalamic D5 receptor constitutive activity alleviates abnormal electrical activity and reverses motor impairment in a rat model of Parkinson's disease | journal = Journal of Neuroscience | volume = 33 | issue = 37 | pages = 14840–9 | year = 2013 | pmid = 24027284 | doi = 10.1523/JNEUROSCI.0453-13.2013 | pmc = 6705171 | doi-access = free }}

• 4-Chloro-7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecin-3-ol: antagonist, moderate binding selectivity over D₁{{cite journal | vauthors = Mohr P, Decker M, Enzensperger C, Lehmann J | title = Dopamine/serotonin receptor ligands. 12(1): SAR studies on hexahydro-dibenz[d,g]azecines lead to 4-chloro-7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecin-3-ol, the first picomolar D₅-selective dopamine-receptor antagonist | journal = J. Med. Chem. | volume = 49 | issue = 6 | pages = 2110–2116 | year = 2006 | pmid = 16539400 | doi = 10.1021/jm051237e }}

Image:4-Chloro-7-methyl-5,6,7,8,9,14-hexahydrodibenz-d,g-azecin-3-ol.png

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• SCH 23390

D₅ receptor has been shown to form heteromers with D₂ receptors. Co-activation of these receptors within the heteromer triggers increase in intracellular calcium. This calcium signaling is dependent on Gq-11 protein signaling and phospholipase C, as well as on the influx of extracellular calcium.{{cite journal | vauthors = So CH, Verma V, Alijaniaram M, Cheng R, Rashid AJ, O'Dowd BF, George SR | title = Calcium signaling by dopamine D5 receptor and D5-D2 receptor hetero-oligomers occurs by a mechanism distinct from that for dopamine D1-D2 receptor hetero-oligomers | journal = Molecular Pharmacology | volume = 75 | issue = 4 | pages = 843–54 | year = 2009 | pmid = 19171671 | pmc = 2684927 | doi = 10.1124/mol.108.051805 }} Heteromers between D₂ and D₅ receptors are formed by adjacent arginines in ic3 (third cytoplasmic loop{{cite journal | vauthors = Ulfers AL, McMurry JL, Kendall DA, Mierke DF | title = Structure of the third intracellular loop of the human cannabinoid 1 receptor | journal = Biochemistry | volume = 41 | issue = 38 | pages = 11344–50 | year = 2002 | pmid = 12234176 | doi=10.1021/bi0259610}}) of D₂ receptor and three adjacent c-terminus glutamic acids in D₅ receptor. Heteromerization of ₂ and D₅ receptors can be disrupted through changes of single amino acids in the c-terminus of the D₅ receptor.

Dopamine receptor D₅ has been shown to interact with GABRG2.{{cite journal | vauthors = Liu F, Wan Q, Pristupa ZB, Yu XM, Wang YT, Niznik HB | title = Direct protein–protein coupling enables cross-talk between dopamine D5 and gamma-aminobutyric acid A receptors | journal = Nature | volume = 403 | issue = 6767 | pages = 274–80 | year = 2000 | pmid = 10659839 | doi = 10.1038/35002014 | bibcode = 2000Natur.403..274L | s2cid = 4415918 }}

The high degree of homology between D₅ and D₁ receptors and their affinity for drugs with similar pharmacological profile complicate distinguishing between them in research. Antibody staining these two receptors separately is suggested to be inefficient.{{cite journal | vauthors = Missale C, Fiorentini C, Collo G, Spano P | title = The neurobiology of dopamine receptors: Evolution from the dual concept to heterodimer complexes | journal = Journal of Receptors and Signal Transduction | volume = 30 | issue = 5 | pages = 347–54 | year = 2010 | pmid = 20684667 | doi = 10.3109/10799893.2010.506192 | s2cid = 11317445 }} However, expression of D₅ receptors has been assessed using immunohistochemistry. In this technique, two peptides were obtained from third extracellular loop and third intracellular loop of the receptor, and antisera were developed for staining the receptor in frozen mouse brain tissue. A method involving mRNA probes for in situ hybridization has been developed, which allowed to separately examine the expression of D₁ and D₅ receptors in the mouse brain.

DRD5 knockout mice can be obtained by crossing 129/SvJ1 and C57BL/6J mice. D₅ receptor can also be inactivated in an animal model by flanking the DRD5 gene with loxP site, allowing to generate tissue or animal lacking functional D₅ receptors.{{cite journal | vauthors = Heyer J, Xiao Q, Bugaj-Gaweda B, Ramboz S, Unterbeck A | title = Conditional inactivation of the dopamine receptor 5 gene: Flanking the Drd5 gene with loxP sites | journal = Genesis | volume = 32 | issue = 2 | pages = 102–4 | year = 2002 | pmid = 11857790 | doi = 10.1002/gene.10069 | doi-access = free }} The expression of D₅ receptor in vitro can also be silenced using antisense oligonucleotides.{{cite journal | vauthors = Wang S, Lu X, Yang J, Wang H, Chen C, Han Y, Ren H, Zheng S, He D, Zhou L, Asico LD, Wang WE, Jose PA, Zeng C | title = Regulation of renalase expression by D5 dopamine receptors in rat renal proximal tubule cells | journal = AJP: Renal Physiology | volume = 306 | issue = 6 | pages = F588–96 | year = 2014 | pmid = 24500688 | pmc = 3949042 | doi = 10.1152/ajprenal.00196.2013 }}

• Dopamine receptor

{{Reflist|35em}}

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• {{cite journal | vauthors = Grandy DK, Allen LJ, Zhang Y, Magenis RE, Civelli O | title = Chromosomal localization of three human D5 dopamine receptor genes | journal = Genomics | volume = 13 | issue = 4 | pages = 968–973 | year = 1992 | pmid = 1387108 | doi = 10.1016/0888-7543(92)90009-H }}
• {{cite journal | vauthors = Eubanks JH, Altherr M, Wagner-McPherson C, McPherson JD, Wasmuth JJ, Evans GA | title = Localization of the D5 dopamine receptor gene to human chromosome 4p15.1-p15.3, centromeric to the Huntington's disease locus | journal = Genomics | volume = 12 | issue = 3 | pages = 510–516 | year = 1992 | pmid = 1532789 | doi = 10.1016/0888-7543(92)90442-U }}
• {{cite journal | vauthors = Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB | title = Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1 | journal = Nature | volume = 350 | issue = 6319 | pages = 614–619 | year = 1991 | pmid = 1826762 | doi = 10.1038/350614a0 | bibcode = 1991Natur.350..614S | s2cid = 4373022 }}
• {{cite journal | vauthors = Tiberi M, Jarvie KR, Silvia C, Falardeau P, Gingrich JA, Godinot N, Bertrand L, Yang-Feng TL, Fremeau RT, Caron MG | title = 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 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 17 | pages = 7491–7495 | year = 1991 | pmid = 1831904 | pmc = 52326 | doi = 10.1073/pnas.88.17.7491 | bibcode = 1991PNAS...88.7491T | doi-access = free }}
• {{cite journal | vauthors = Grandy DK, Zhang YA, Bouvier C, Zhou QY, Johnson RA, Allen L, Buck K, Bunzow JR, Salon J, Civelli O | title = Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 20 | pages = 9175–9179 | year = 1991 | pmid = 1833775 | pmc = 52675 | doi = 10.1073/pnas.88.20.9175 | bibcode = 1991PNAS...88.9175G | doi-access = free }}
• {{cite journal | vauthors = Weinshank RL, Adham N, Macchi M, Olsen MA, Branchek TA, Hartig PR | title = Molecular cloning and characterization of a high affinity dopamine receptor (D1 beta) and its pseudogene | journal = J. Biol. Chem. | volume = 266 | issue = 33 | pages = 22427–35 | year = 1991 | doi = 10.1016/S0021-9258(18)54590-7 | pmid = 1834671 | doi-access = free }}
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{{refend}}

• {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2260 | title = Dopamine Receptors: D₁ | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | access-date = 4 December 2008 | archive-date = 31 December 2014 | archive-url = https://web.archive.org/web/20141231160117/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2260 | url-status = dead }}
• {{MeshName|DRD5+protein,+human}}

{{NLM content}}

{{G protein-coupled receptors}}

Category:Dopamine receptors