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Dopamine receptor D5
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<h2 id="function">Function</h2> <p>D5 receptor is a subtype of the dopamine receptor that has a 10-fold higher affinity for dopamine than the <a href="/facts/Dopamine_receptor_D1/fkWRTblS">D1</a> subtype.<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a> The D5 subtype is a <a href="/facts/G-protein_coupled_receptor/0arUMkQc">G-protein coupled receptor</a>, which promotes synthesis of <a href="/facts/Cyclic_adenosine_monophosphate/flK2vwUe">cAMP</a> by <a href="/facts/Adenylyl_cyclase/WnCSuV96">adenylyl cyclase</a> via activation of <a href="/facts/Gs_alpha_subunit/IVryW6op">Gαs/olf family of G proteins</a>.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a><a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> Both D5 and D1 subtypes activate <a href="/facts/Adenylyl_cyclase/WnCSuV96">adenylyl cyclase</a>. D1 receptors were shown to stimulate monophasic <a href="/facts/Dose-response_relationship/DLcuLdHc">dose-dependent</a> accumulation of cAMP in response to <a href="/facts/Dopamine/5gNy8Xkd">dopamine</a>, 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.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> </p><p>Activation of D5 receptors is shown to promote expression of <a href="/facts/Brain-derived_neurotrophic_factor/1v80e05e">brain-derived neurotrophic factor</a> and increase <a href="/facts/Phosphorylation/LXUEEeIL">phosphorylation</a> of <a href="/facts/Protein_kinase_B/odL6duk1">protein kinase B</a> in rat and mice <a href="/facts/Prefrontal_cortex/dypYIrwx">prefrontal cortex</a> neurons.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> </p><p><a href="/facts/In_vitro/evp3hAX6">In vitro</a>, D5 receptors show high constitutive activity that is independent of binding any <a href="/facts/Agonist/nz8U5NNp">agonists</a>.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> </p> <h2 id="primary-structure">Primary structure</h2> <p>D5 receptor is highly <a href="/facts/Homology_(biology)/muctKlyT">homologous</a> to the <a href="/facts/Dopamine_receptor_D1/fkWRTblS">D1</a> receptor. Their <a href="/facts/Peptide_sequence/QNBoERdu">amino acid sequences</a> are 49%<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> to 80%<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> identical. D5 receptor has a long <a href="/facts/C-terminus/ws4scHgT">C-terminus</a> of 93 <a href="/facts/Amino_acid/WDxYwBny">amino acids</a>, accounting for 26% of the entire protein. In spite of the high degree of homology between D5 and <a href="/facts/Dopamine_receptor_D1/fkWRTblS">D1</a> receptors, their c-terminus tails have little similarity.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> </p> <h2 id="chromosomal-location">Chromosomal location</h2> <p>In humans, D5 receptor is encoded on the <a href="/facts/Chromosome_4_(human)/B4lT0YrJ">chromosome 4p15.1–p15.3</a>.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> The gene lacks introns<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> and encodes a product of 477 <a href="/facts/Amino_acid/WDxYwBny">amino acids</a>.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> 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 <a href="/facts/Reading_frame/6Ugt2vUe">in-frame</a> <a href="/facts/Stop_codon/1yuAkq9X">stop codons</a> that prevent these genes from transcribing a functional protein.<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> </p> <h2 id="expression">Expression</h2> <h3>Central nervous system</h3> <p>D5 receptor is expressed more widely in the <a href="/facts/Central_nervous_system/k8I6To97">CNS</a> than its close structural homolog <a href="/facts/Dopamine_receptor_D1/fkWRTblS">dopamine receptor D1</a>.<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> It is found in neurons in <a href="/facts/Amygdala/AAy2mHb5">amygdala</a>, <a href="/facts/Frontal_cortex/RvokInmf">frontal cortex</a>, <a href="/facts/Hippocampus/X7CqbP8X">hippocampus</a>, <a href="/facts/Striatum/MjNnTjSd">striatum</a>, <a href="/facts/Thalamus/UHDtUStc">thalamus</a>, <a href="/facts/Hypothalamus/lCkNt1bM">hypothalamus</a>, <a href="/facts/Basal_forebrain/eFB15xYw">basal forebrain</a>, <a href="/facts/Cerebellum/kBRS2Lou">cerebellum</a>,<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> and <a href="/facts/Midbrain/NXpE9WXV">midbrain</a>.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> Dopamine receptor D5 is exclusively expressed by large aspiny neurons in <a href="/facts/Neostriatum/MjNnTjSd">neostriatum</a> of primates, which are typically <a href="/facts/Cholinergic/51ttI8RK">cholinergic</a> <a href="/facts/Interneuron/1uca9khG">interneurons</a>.<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> Within a cell, D5 receptors are found on the membrane of <a href="/facts/Perikaryon/L8aDnXKr">soma</a> and proximal <a href="/facts/Dendrite/bwv8MABY">dendrites</a>.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> They are also sometimes located in the <a href="/facts/Neuropil/35w4jmL0">neuropil</a> in the <a href="/facts/Olfactory_bulb/P2xEB4es">olfactory region</a>, <a href="/facts/Superior_colliculus/UReX4bqE">superior colliculus</a>, and <a href="/facts/Cerebellum/kBRS2Lou">cerebellum</a>.<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> D5 receptor is also found in <a href="/facts/Striatum/MjNnTjSd">striatal</a> <a href="/facts/Astrocyte/PBUuHKzS">astrocytes</a> of the <a href="/facts/Rat/5rn6uEKM">rat</a> <a href="/facts/Basal_ganglia/d9mbF6p3">basal ganglia</a>.<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> </p><p>The receptors of this subtype are also expressed on <a href="/facts/Dendritic_cell/19KBuKFK">dendritic cells</a> and <a href="/facts/T_helper_cell/nhwAYkDj">T helper cells</a>.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> </p> <h3>Kidney</h3> <p>D5 receptors are expressed in <a href="/facts/Kidney/HBspPrv9">kidneys</a> and are involved in regulation of <a href="/facts/Sodium/eYuSPu2V">sodium</a> excretion. They are located on <a href="/facts/Proximal_convoluted_tubule/mkezjse0">proximal convoluted tubules</a>, and their activation suppresses the activity of <a href="/facts/Sodium%25E2%2580%2593hydrogen_antiporter/eea96gU6">sodium–hydrogen antiporter</a> and <a href="/facts/Na%252B%2fK%252B-ATPase/SuA4d4Na">Na+/K+-ATPase</a>, preventing reabsorption of sodium.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a> D5 receptors are thought to positively regulate expression of <a href="/facts/Renalase/VgAPugsG">renalase</a>.<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> Their faulty functioning in nephrons can contribute to <a href="/facts/Hypertension/wlAvBfcf">hypertension</a>.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a><a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> </p> <h2 id="clinical-significance">Clinical significance</h2> <h3>Learning and memory</h3> <p>D5 receptor participates in the synaptic processes that underlie learning and memory. These receptors participate in the formation of <a href="/facts/Long-term_depression/s9e91167">LTD</a> in rodent <a href="/facts/Striatum/MjNnTjSd">striatum</a>, which is opposite to the <a href="/facts/Dopamine_receptor_D1/fkWRTblS">D1 receptor</a> involvement with the formation of <a href="/facts/Long-term_potentiation/AbuJmBeo">LTP</a> in the same brain region.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> D5 receptors are also associated with the consolidation of fear memories in <a href="/facts/Amygdala/AAy2mHb5">amygdala</a>. It has been shown that <a href="/facts/Muscarinic_acetylcholine_receptor_m1/ne0YBBqI">M1-Muscarinic receptors</a> cooperate with D5 receptors and <a href="/facts/Beta-2_adrenergic_receptor/erywpzGl">beta-2 adrenergic receptors</a> to <a href="/facts/Memory_consolidation/n9JtsvIB">consolidate</a> cued fear memory. It is suggested that these <a href="/facts/G_protein-coupled_receptor/0arUMkQc">G protein-coupled receptors</a> redundantly activate <a href="/facts/Phospholipase_C/Cuo6V7gU">phospholipase C</a> in <a href="/facts/Basolateral_amygdala/U8XImwsF">basolateral amygdala</a>. One effect of the activation of phospholipase C is deactivation of <a href="/facts/KCNQ5/LIBaeeK3">KCNQ channels</a>.<a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a> Since KCNQ channels conduct <a href="/facts/M_current/w6g5P0u8">M current</a> that raises the threshold for <a href="/facts/Action_potential/Sz8yCRqx">action potential</a>,<a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> deactivation of these channels leads to increased neuronal excitability and enhanced memory consolidation.<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a> </p><p>D5 receptors may be required for <a href="/facts/Long-term_potentiation/AbuJmBeo">long-term potentiation</a> at the <a href="/facts/Synapse/vdMRJCUn">synapse</a> between <a href="/facts/Perforant_path/oMbxdKpz">medial perforant path</a> and <a href="/facts/Dentate_gyrus/S8a0mopL">dentate gyrus</a> in <a href="/facts/Murinae/7ds8prdo">murine</a> <a href="/facts/Hippocampus/X7CqbP8X">hippocampal formation</a>.<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> </p> <h3>Addiction</h3> <h4>Smoking</h4> <p><a href="/facts/Polymorphism_(biology)/lf32kgfV">Polymorphisms</a> 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 <a href="/facts/Haplotype/0W2SEdu4">haplotype</a> of DRD5 that is protective against initiation of smoking.<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a> </p> <h3>ADHD</h3> <p><a href="/facts/Tandem_repeat/V40yCKFJ">Dinucleotide repeats</a> of DRD5 gene are associated with <a href="/facts/Attention_Deficit_Hyperactivity_Disorder/uSqjIyhd">ADHD</a> 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 <a href="/facts/Risk_factor/N0YTUyer">risk factor</a> for it.<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> 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.<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> Another allele of DRD5 that is moderately associated with ADHD susceptibility is 150 bp.<a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> In a <a href="/facts/Animal_model/xPBrtWUX">rat model</a> of ADHD, low density of D5 was found in the <a href="/facts/Hippocampus/X7CqbP8X">hippocampal</a> <a href="/facts/Pyramidal_cell/T8MTBq8b">pyramidal cell</a> <a href="/facts/Perikaryon/L8aDnXKr">somas</a>. Deficiency in D5 receptors may contribute to <a href="/facts/Learning_disability/HJoAq92N">learning problems</a> that may be associated with ADHD.<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a> </p> <h3>Parkinson's disease</h3> <p>D5 receptors may be involved in <a href="/facts/Bursting/6u4F6c9M">burst firing</a> of <a href="/facts/Subthalamic_nucleus/2YJLz5rN">subthalamic nucleus</a> neurons in <a href="/facts/Oxidopamine/J41UtvL0">6-OHDA</a> rat model of <a href="/facts/Parkinson%2527s_disease/xpekKj6x">Parkinson's disease</a>. In this animal model, blockage of D5 receptors with <a href="/facts/Flupentixol/lx3rT6tU">flupentixol</a> reduces burst firing and improves motor deficits.<a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a> 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.<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a><a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> </p> <h3>Schizophrenia</h3> <p>Several polymorphisms in DRD5 genes have been associated with susceptibility to <a href="/facts/Schizophrenia/FMP4lQ57">schizophrenia</a>. The 148 bp allele of DRD5 was linked to increased risk of schizophrenia.<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a> Some <a href="/facts/Single-nucleotide_polymorphisms/Qy5Y2wom">single-nucleotide polymorphisms</a> in this gene, including changes in rs77434921, rs1800762, rs77434921, and rs1800762, in northern <a href="/facts/Han_Chinese/gMl0sKy0">Han Chinese</a> population.<a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a> </p> <h3>Locomotion</h3> <p>D5 receptor is believed to participate in modulation of <a href="/facts/Stimulant/nmBdAXM5">psychostimulant</a>-induced <a href="/facts/Animal_locomotion/trhhYTVR">locomotion</a>. Mice lacking D5 receptors show increased motor response to administration of <a href="/facts/Methamphetamine/vS1jloMe">methamphetamine</a> than <a href="/facts/Wild_type/Rr0vGvM0">wild type</a> mice,<a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> which suggests that these receptors have a role in controlling motor activity. </p> <h3>Regulation of blood pressure</h3> <p>D5 receptor may be involved in modulation of the neuronal pathways that regulate <a href="/facts/Blood_pressure/VtqqSM2J">blood pressure</a>. Mice lacking this receptor in their brains showed <a href="/facts/Hypertension/wlAvBfcf">hypertension</a> and elevated <a href="/facts/Blood_pressure/VtqqSM2J">blood pressure</a>, which may have been caused by increased <a href="/facts/Sympathetic_nervous_system/hs8psNRd">sympathetic tone</a>.<a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a> D5 receptors that are expressed in kidneys are also involved in the regulation of blood pressure via modulating expression of <a href="/facts/Renalase/VgAPugsG">renalase</a> and excretion of <a href="/facts/Sodium/eYuSPu2V">sodium</a>, and disturbance of these processes can contribute to hypertension as well.<a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a> </p> <h3>Immunity</h3> <p>D5 receptors negatively regulate production of <a href="/facts/Interferon_gamma/r51CXVph">IFNγ</a> by <a href="/facts/Natural_killer_cell/A3THWxrJ">NK cells</a>. The expression of D5 receptors was shown to be upregulated in NK cells in response to prolonged stimulation with <a href="/facts/Recombinant_DNA/dT3PL7M6">recombinant</a> <a href="/facts/Interleukin_2/hH1DXu2W">interleukin 2</a>. This upregulation inhibits <a href="/facts/Cell_proliferation/Jp3hWo2t">proliferation</a> of the NK cells and suppresses synthesis of IFNγ. Activation of D5 prevents p50, part of <a href="/facts/NFKB1/ocSAtPvP">NF-κB protein complex</a>, from <a href="/facts/Repressor/qGBBQwqS">repressing the transcription</a> of <a href="/facts/Mir-29_microRNA_precursor/hTM5nvwy">miRNA 29a</a>. Because miRNA29a targets <a href="/facts/MRNA/oUL6qxQn">mRNA</a> of IFNγ, the expression of IFNγ protein is diminished.<a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a> </p><p>D5 receptors are involved in activation and differentiation of <a href="/facts/T_helper_17_cell/V3TmUNSX">T helper 17 cells</a>. Specifically, these receptors play a role in polarization of <a href="/facts/T_helper_cell/nhwAYkDj">CD4+ T-cells</a> into the T helper 17 cells by modulating secretion of <a href="/facts/Interleukin_12/rCttxoLL">interleukin 12</a> and <a href="/facts/Interleukin_23/tsVFeqRs">interleukin 23</a> in response to stimulation with <a href="/facts/Lipopolysaccharide/Ch967TXw">LPS</a>.<a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a> </p> <h2 id="ligands">Ligands</h2> <p>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 D1/5 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. </p><p>D5 receptors show higher affinity for agonists and lower affinity for antagonists than D1 receptors.<a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a> </p> <h3>Agonists</h3> <ul><li><a href="/facts/Dihydrexidine/1H9ewY2E">Dihydrexidine</a></li> <li><a href="/facts/Rotigotine/B1jkM4CN">Rotigotine</a><a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a></li> <li><a href="/facts/SKF-83%2c959/w3oEc6WK">SKF-83,959</a><a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a></li> <li><a href="/facts/Stepholidine/ecA0r9Uv">Stepholidine</a><a class="footnote-ref" id="fnref:50" href="#fn:50"><sup>50</sup></a></li> <li><a href="/facts/Fenoldopam/EsEpaXzg">Fenoldopam</a><a class="footnote-ref" id="fnref:51" href="#fn:51"><sup>51</sup></a></li></ul> <h3>Inverse agonists</h3> <ul><li><a href="/facts/Flupentixol/lx3rT6tU">Flupentixol</a><a class="footnote-ref" id="fnref:52" href="#fn:52"><sup>52</sup></a></li></ul> <h3>Antagonists</h3> <ul><li>4-Chloro-7-methyl-5,6,7,8,9,14-hexahydrodibenz[<i>d,g</i>]azecin-3-ol: antagonist, moderate binding selectivity over D1<a class="footnote-ref" id="fnref:53" href="#fn:53"><sup>53</sup></a></li></ul> <ul><li><a href="/facts/SCH_23390/brLQqxtW">SCH 23390</a><a class="footnote-ref" id="fnref:54" href="#fn:54"><sup>54</sup></a></li></ul> <h2 id="proteinprotein-interactions">Protein–protein interactions</h2> <p>D5 receptor has been shown to form <a href="/facts/Heteromer/hu87Tm8d">heteromers</a> with <a href="/facts/Dopamine_receptor_D2/SmmP3QyU">D2 receptors</a>. Co-activation of these receptors within the heteromer triggers increase in <a href="/facts/Calcium_signaling/2zzv1pm6">intracellular calcium</a>. This calcium signaling is dependent on <a href="/facts/Gq_alpha_subunit/Y8TVuq2U">Gq-11 protein signaling</a> and <a href="/facts/Phospholipase_C/Cuo6V7gU">phospholipase C</a>, as well as on the influx of extracellular <a href="/facts/Calcium/hf252CC0">calcium</a>.<a class="footnote-ref" id="fnref:55" href="#fn:55"><sup>55</sup></a> Heteromers between D2 and D5 receptors are formed by adjacent <a href="/facts/Arginine/y49Hdf1e">arginines</a> in ic3 (third cytoplasmic loop<a class="footnote-ref" id="fnref:56" href="#fn:56"><sup>56</sup></a>) of D2 receptor and three adjacent <a href="/facts/C-terminus/ws4scHgT">c-terminus</a> <a href="/facts/Glutamic_acid/7oXbNcvu">glutamic acids</a> in D5 receptor. Heteromerization of 2 and D5 receptors can be disrupted through changes of single amino acids in the <a href="/facts/C-terminus/ws4scHgT">c-terminus</a> of the D5 receptor.<a class="footnote-ref" id="fnref:57" href="#fn:57"><sup>57</sup></a> </p><p>Dopamine receptor D5 has been shown to <a href="/facts/Protein%25E2%2580%2593protein_interaction/etvm9Wmg">interact</a> with <a href="/facts/GABRG2/SyPxa1If">GABRG2</a>.<a class="footnote-ref" id="fnref:58" href="#fn:58"><sup>58</sup></a> </p> <h2 id="experimental-methods">Experimental methods</h2> <p>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. <a href="/facts/Immunostaining/hVg7s9nX">Antibody staining</a> these two receptors separately is suggested to be inefficient.<a class="footnote-ref" id="fnref:59" href="#fn:59"><sup>59</sup></a> However, expression of D5 receptors has been assessed using <a href="/facts/Immunohistochemistry/knPpmAFf">immunohistochemistry</a>. In this technique, two <a href="/facts/Peptide/C4ltc7UG">peptides</a> were obtained from third extracellular loop and third intracellular loop of the receptor, and <a href="/facts/Antiserum/zt7McfLV">antisera</a> were developed for staining the receptor in frozen <a href="/facts/Mouse_brain/b251sw7h">mouse brain</a> tissue.<a class="footnote-ref" id="fnref:60" href="#fn:60"><sup>60</sup></a> A method involving <a href="/facts/Messenger_RNA/oUL6qxQn">mRNA</a> probes for <a href="/facts/In_situ_hybridization/RFKJedCS">in situ hybridization</a> has been developed, which allowed to separately examine the expression of D1 and D5 receptors in the mouse brain.<a class="footnote-ref" id="fnref:61" href="#fn:61"><sup>61</sup></a> </p><p>DRD5 <a href="/facts/Gene_knockout/RJTMDbUR">knockout</a> mice can be obtained by crossing 129/SvJ1 and <a href="/facts/C57BL%2f6J/XTu9PF0o">C57BL/6J</a> mice.<a class="footnote-ref" id="fnref:62" href="#fn:62"><sup>62</sup></a> D5 receptor can also be inactivated in an <a href="/facts/Animal_model/xPBrtWUX">animal model</a> by flanking the DRD5 gene with <a href="/facts/Cre-Lox_recombination/Ha9d2CKT">loxP site</a>, allowing to generate tissue or animal lacking functional D5 receptors.<a class="footnote-ref" id="fnref:63" href="#fn:63"><sup>63</sup></a> The expression of D5 receptor <i>in vitro</i> can also be silenced using <a href="/facts/Oligonucleotide/Gc99fPnC">antisense oligonucleotides</a>.<a class="footnote-ref" id="fnref:64" href="#fn:64"><sup>64</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Dopamine_receptor/fgsjJwkL">Dopamine receptor</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998). "Dopamine receptors: from structure to function". <i>Physiol. Rev</i>. 78 (1): 189–225. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1152%2Fphysrev.1998.78.1.189">10.1152/physrev.1998.78.1.189</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9457173">9457173</a>.</li> <li>Grandy DK, Allen LJ, Zhang Y, Magenis RE, Civelli O (1992). "Chromosomal localization of three human D5 dopamine receptor genes". <i>Genomics</i>. 13 (4): 968–973. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0888-7543%2892%2990009-H">10.1016/0888-7543(92)90009-H</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1387108">1387108</a>.</li> <li>Eubanks JH, Altherr M, Wagner-McPherson C, McPherson JD, Wasmuth JJ, Evans GA (1992). "Localization of the D5 dopamine receptor gene to human chromosome 4p15.1-p15.3, centromeric to the Huntington's disease locus". <i>Genomics</i>. 12 (3): 510–516. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2F0888-7543%2892%2990442-U">10.1016/0888-7543(92)90442-U</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1532789">1532789</a>.</li> <li>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". <i>Nature</i>. 350 (6319): 614–619. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1991Natur.350..614S">1991Natur.350..614S</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2F350614a0">10.1038/350614a0</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1826762">1826762</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:4373022">4373022</a>.</li> <li>Tiberi M, Jarvie KR, Silvia C, Falardeau P, Gingrich JA, Godinot N, Bertrand L, Yang-Feng TL, Fremeau RT, Caron MG (1991). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC52326">"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"</a>. <i>Proc. Natl. Acad. Sci. U.S.A</i>. 88 (17): 7491–7495. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1991PNAS...88.7491T">1991PNAS...88.7491T</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.88.17.7491">10.1073/pnas.88.17.7491</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC52326">52326</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1831904">1831904</a>.</li> <li>Grandy DK, Zhang YA, Bouvier C, Zhou QY, Johnson RA, Allen L, Buck K, Bunzow JR, Salon J, Civelli O (1991). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC52675">"Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes"</a>. <i>Proc. Natl. Acad. Sci. U.S.A</i>. 88 (20): 9175–9179. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/1991PNAS...88.9175G">1991PNAS...88.9175G</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.88.20.9175">10.1073/pnas.88.20.9175</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC52675">52675</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1833775">1833775</a>.</li> <li>Weinshank RL, Adham N, Macchi M, Olsen MA, Branchek TA, Hartig PR (1991). <a href="https://doi.org/10.1016%2FS0021-9258%2818%2954590-7">"Molecular cloning and characterization of a high affinity dopamine receptor (D1 beta) and its pseudogene"</a>. <i>J. Biol. Chem</i>. 266 (33): 22427–35. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0021-9258%2818%2954590-7">10.1016/S0021-9258(18)54590-7</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/1834671">1834671</a>.</li> <li>Sobell JL, Lind TJ, Sigurdson DC, Zald DH, Snitz BE, Grove WM, Heston LL, Sommer SS (1995). "The D5 dopamine receptor gene in schizophrenia: identification of a nonsense change and multiple missense changes but lack of association with disease". <i>Hum. Mol. Genet</i>. 4 (4): 507–514. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1093%2Fhmg%2F4.4.507">10.1093/hmg/4.4.507</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7633397">7633397</a>.</li> <li>Beischlag TV, Marchese A, Meador-Woodruff JH, Damask SP, O'Dowd BF, Tyndale RF, van Tol HH, Seeman P, Niznik HB (1995). "The human dopamine D5 receptor gene: cloning and characterization of the 5'-flanking and promoter region". <i>Biochemistry</i>. 34 (17): 5960–5970. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1021%2Fbi00017a025">10.1021/bi00017a025</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7727453">7727453</a>.</li> <li>Sherrington R, Mankoo B, Attwood J, Kalsi G, Curtis D, Buetow K, Povey S, Gurling H (1994). "Cloning of the human dopamine D5 receptor gene and identification of a highly polymorphic microsatellite for the DRD5 locus that shows tight linkage to the chromosome 4p reference marker RAF1P1". <i>Genomics</i>. 18 (2): 423–425. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1006%2Fgeno.1993.1489">10.1006/geno.1993.1489</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8288248">8288248</a>.</li> <li>Sidhu A, Kimura K, Uh M, White BH, Patel S (1998). <a href="https://doi.org/10.1046%2Fj.1471-4159.1998.70062459.x">"Multiple coupling of human D5 dopamine receptors to guanine nucleotide binding proteins Gs and Gz"</a>. <i>J. Neurochem</i>. 70 (6): 2459–2467. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1046%2Fj.1471-4159.1998.70062459.x">10.1046/j.1471-4159.1998.70062459.x</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9603210">9603210</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:35877239">35877239</a>.</li> <li>Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES (1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes". <i>Nat. Genet</i>. 22 (3): 231–238. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2F10290">10.1038/10290</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10391209">10391209</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:195213008">195213008</a>.</li> <li>Liu F, Wan Q, Pristupa ZB, Yu XM, Wang YT, Niznik HB (2000). "Direct protein–protein coupling enables cross-talk between dopamine D5 and gamma-aminobutyric acid A receptors". <i>Nature</i>. 403 (6767): 274–280. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/2000Natur.403..274L">2000Natur.403..274L</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2F35002014">10.1038/35002014</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10659839">10659839</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:4415918">4415918</a>.</li> <li>Misbahuddin A, Placzek MR, Chaudhuri KR, Wood NW, Bhatia KP, Warner TT (2004). 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International Union of Basic and Clinical Pharmacology. Archived from <a href="http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2260">the original</a> on 31 December 2014. Retrieved 4 December 2008.</li> <li><a href="https://meshb.nlm.nih.gov/record/ui?name=DRD5+protein%2C+human">DRD5+protein,+human</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li></ul> <p><i>This article incorporates text from the <a href="/facts/United_States_National_Library_of_Medicine/Hzty0MCX">United States National Library of Medicine</a>, which is in the <a href="/facts/Public_domain/YWKMDKw4">public domain</a>.</i> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Polymeropoulos MH, Xiao H, Merril CR (March 1992). "The human D5 dopamine receptor (DRD5) maps on chromosome 4". Genomics. 11 (3): 777–778. doi:10.1016/0888-7543(91)90091-R. PMID 1774076. <a href="https://zenodo.org/record/1258583" target="_blank">https://zenodo.org/record/1258583</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>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. Bibcode:1991Natur.350..614S. doi:10.1038/350614a0. PMID 1826762. S2CID 4373022. <a href="/wiki/Bibcode_(identifier)" target="_blank">/wiki/Bibcode_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Beaulieu JM, Gainetdinov RR (2011). "The physiology, signaling, and pharmacology of dopamine receptors". Pharmacol. Rev. 63 (1): 182–217. doi:10.1124/pr.110.002642. PMID 21303898. S2CID 2545878. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Mello, F. G. (October 1978). "The Ontogeny of Dopamine-Dependent Increase of Adenosine 3',5'-Cyclic Monophosphate in the Chick Retina". Journal of Neurochemistry. 31 (4): 1049–1053. doi:10.1111/j.1471-4159.1978.tb00146.x. ISSN 0022-3042. PMID 212530. S2CID 84297833. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>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 (20): 9175–9. Bibcode:1991PNAS...88.9175G. doi:10.1073/pnas.88.20.9175. PMC 52675. PMID 1833775. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC52675" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC52675</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Perreault ML, Jones-Tabah J, O'Dowd BF, George SR (2013). "A physiological role for the dopamine D5 receptor as a regulator of BDNF and Akt signalling in rodent prefrontal cortex". The International Journal of Neuropsychopharmacology. 16 (2): 477–83. doi:10.1017/S1461145712000685. PMC 3802523. PMID 22827965. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3802523" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3802523</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Tiberi M, Caron MG (1994). "High agonist-independent activity is a distinguishing feature of the dopamine D1B receptor subtype". J. Biol. Chem. 269 (45): 27925–31. doi:10.1016/S0021-9258(18)46876-7. PMID 7525564. <a href="https://doi.org/10.1016%2FS0021-9258%2818%2946876-7" target="_blank">https://doi.org/10.1016%2FS0021-9258%2818%2946876-7</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>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. Bibcode:1991Natur.350..614S. doi:10.1038/350614a0. PMID 1826762. S2CID 4373022. <a href="/wiki/Bibcode_(identifier)" target="_blank">/wiki/Bibcode_(identifier)</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>O'Dowd BF, Nguyen T, Ji X, George SR (2013). "D5 dopamine receptor carboxyl tail involved in D5-D2 heteromer formation". Biochemical and Biophysical Research Communications. 431 (3): 586–9. doi:10.1016/j.bbrc.2012.12.139. PMC 3744868. PMID 23318175. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744868" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744868</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>O'Dowd BF, Nguyen T, Ji X, George SR (2013). "D5 dopamine receptor carboxyl tail involved in D5-D2 heteromer formation". Biochemical and Biophysical Research Communications. 431 (3): 586–9. doi:10.1016/j.bbrc.2012.12.139. PMC 3744868. PMID 23318175. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744868" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744868</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Eubanks JH, Altherr M, Wagner-McPherson C, McPherson JD, Wasmuth JJ, Evans GA (1992). "Localization of the D5 dopamine receptor gene to human chromosome 4p15.1-p15.3, centromeric to the Huntington's disease locus". Genomics. 12 (3): 510–6. doi:10.1016/0888-7543(92)90442-u. PMID 1532789. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>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 (20): 9175–9. Bibcode:1991PNAS...88.9175G. doi:10.1073/pnas.88.20.9175. PMC 52675. PMID 1833775. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC52675" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC52675</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>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. Bibcode:1991Natur.350..614S. doi:10.1038/350614a0. 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