多巴胺受體D₂

多巴胺受體D2
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	6CM4
識別號
别名	DRD2；, D2DR, D2R, dopamine receptor D2
外部ID	OMIM：126450 MGI：94924 HomoloGene：22561 GeneCards：DRD2
相關疾病
	重性抑郁障碍[1]
為以下藥物的標靶
	remoxipride[2]
	benzquinamide、LP-12、LP-211、LP-44、罗匹尼罗、羅替戈汀、维拉佐酮、7-hydroxy-2-(di-N-propylamino)tetralin、溴隱亭、多巴胺、培高利特、普拉克索、quinelorane、quinpirole、sumanirole、阿樸嗎啡、阿立哌唑、brexpiprazole、過乳降、麥角乙脲、吡貝地爾、roxindole、特麦角脲、氨磺必利、布南色林、(+)-butaclamol、氯丙嗪、氯氮平、多潘立酮、eticlopride、三氟噻噸、氟奋乃静、氟哌啶醇、L-741,626、洛沙平、mesoridazine、nafadotride、奥氮平、perospirone、奋乃静、匹莫齊特、pipotiazine、普樂明、promazine、喹硫平、raclopride、利培酮、sertindole、舒必利、levosulpiride、三氟拉嗪、齊拉西酮、zotepine[3]
基因位置（人类）
染色体	11號染色體[4]
终止	113,475,691 bp[4]
基因位置（小鼠）
染色体	小鼠9号染色体[5]
终止	49,319,477 bp[5]
RNA表达模式
	; ; ; ;
	查阅更多表达数据
基因本體
分子功能	• protein homodimerization activity; • potassium channel regulator activity; • dopamine neurotransmitter receptor activity, coupled via Gi/Go; • 相同蛋白质结合; • dopamine neurotransmitter receptor activity; • G protein-coupled receptor activity; • 血浆蛋白结合; • signal transducer activity; • adrenergic receptor activity; • dopamine binding; • signaling receptor binding; • ionotropic glutamate receptor binding; • protein heterodimerization activity;
細胞組分	• cytoplasmic vesicle; • sperm flagellum; • endocytic vesicle; • 顶体; • 树突棘; • synaptic vesicle membrane; • 細胞本體; • 细胞膜; • 树突; • ciliary membrane; • 神经末梢; • integral component of membrane; • 突触后致密物质; • 膜; • lateral plasma membrane; • 轴突; • 胞內; • non-motile cilium; • integral component of plasma membrane; • dopaminergic synapse; • glutamatergic synapse; • GABA-ergic synapse; • integral component of postsynaptic membrane; • integral component of presynaptic membrane;
生物學過程	• negative regulation of cell population proliferation; • temperature homeostasis; • adenylate cyclase-inhibiting dopamine receptor signaling pathway; • adenohypophysis development; • circadian regulation of gene expression; • response to toxic substance; • regulation of dopamine secretion; • response to cocaine; • response to amphetamine; • sensory perception of smell; • locomotory behavior; • positive regulation of urine volume; • response to ethanol; • axonogenesis; • response to inactivity; • phospholipase C-activating dopamine receptor signaling pathway; • modulation of chemical synaptic transmission; • 个人仪容; • negative regulation of protein kinase B signaling; • 联想型学习; • positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; • regulation of dopamine uptake involved in synaptic transmission; • regulation of synaptic transmission, GABAergic; • positive regulation of dopamine uptake involved in synaptic transmission; • 訊息傳遞; • Wnt信号通路; • adult walking behavior; • branching morphogenesis of a nerve; • negative regulation of cytosolic calcium ion concentration; • negative regulation of innate immune response; • regulation of phosphoprotein phosphatase activity; • acid secretion; • 进食行为; • positive regulation of G protein-coupled receptor signaling pathway; • response to axon injury; • striatum development; • synaptic transmission, dopaminergic; • nervous system process involved in regulation of systemic arterial blood pressure; • 蠕動; • regulation of long-term neuronal synaptic plasticity; • activation of protein kinase activity; • positive regulation of growth hormone secretion; • regulation of sodium ion transport; • forebrain development; • response to light stimulus; • orbitofrontal cortex development; • 前脉冲抑制; • response to morphine; • response to iron ion; • positive regulation of ERK1 and ERK2 cascade; • 长期记忆; • positive regulation of renal sodium excretion; • negative regulation of insulin secretion; • neuron-neuron synaptic transmission; • intracellular signal transduction; • auditory behavior; • behavioral response to ethanol; • regulation of heart rate; • adenylate cyclase-activating adrenergic receptor signaling pathway; • positive regulation of cytokinesis; • regulation of potassium ion transport; • 色素沉着; • cellular calcium ion homeostasis; • dopamine metabolic process; • response to nicotine; • regulation of MAPK cascade; • response to histamine; • negative regulation of synaptic transmission, glutamatergic; • response to hypoxia; • negative regulation of circadian sleep/wake cycle, sleep; • negative regulation of protein secretion; • synapse assembly; • regulation of locomotion involved in locomotory behavior; • dopamine receptor signaling pathway; • negative regulation of dopamine receptor signaling pathway; • 驚跳反射; • positive regulation of receptor internalization; • protein localization; • arachidonic acid secretion; • positive regulation of transcription by RNA polymerase II; • G protein-coupled receptor internalization; • positive regulation of multicellular organism growth; • positive regulation of long-term synaptic potentiation; • negative regulation of dopamine secretion; • adult behavior; • cerebral cortex GABAergic interneuron migration; • regulation of synapse structural plasticity; • adenylate cyclase-modulating G protein-coupled receptor signaling pathway; • visual learning; • negative regulation of cell migration; • behavioral response to cocaine; • positive regulation of neuroblast proliferation; • negative regulation of blood pressure; • release of sequestered calcium ion into cytosol; • negative regulation of voltage-gated calcium channel activity; • G protein-coupled receptor signaling pathway; • negative regulation of adenylate cyclase activity; • 興奮性動作電位; • negative regulation of protein phosphorylation; • 自噬; • positive regulation of neurogenesis; • negative regulation of cell death; • drinking behavior; • adrenergic receptor signaling pathway; • regulation of neurotransmitter uptake; • postsynaptic modulation of chemical synaptic transmission; • regulation of synaptic vesicle exocytosis;
	Sources:Amigo / QuickGO
直系同源
	1813
	13489
	ENSG00000149295
	ENSMUSG00000032259
	P14416
	P61168
	NM_016574; NM_000795
	NM_010077
	NP_000786; NP_057658; NP_000786.1
	NP_034207
	維基數據

多巴胺受體D₂（，簡稱D2R），為轉譯自 DRD2 基因的一種多巴胺受體蛋白。D2R最早於1975年為Philip Seeman所發現，並將其命名為「抗精神疾患性多巴胺受體」（antipsychotic dopamine receptor）[8]。D2R為所有抗精神病药物的作用標的。

功能

D2R屬於一種多巴胺受體，並會與G_i結合。G_i為G蛋白偶联受体的一種亞型，會抑制腺苷酸环化酶的活性[9]。

在小鼠模式中，齒狀回的neuronal calcium sensor-1（NCS-1）會影響D2R在細胞膜的表現量。這項機制會影響突触可塑性及記憶形成[10]。

在蒼蠅模式中，多巴胺性神經元上的D2R自體受器能避免神經元死亡，進而引發類帕金森氏症的症狀[11]。

同型體

此基因的选择性剪接产生三种不同编码亚型的转录变体。[12]

长形式（D2Lh）具有"规范"的序列，并作为经典突触后蛋白发挥作用。[13]短形式（D2Sh）在突触前作为调节突触间隙中多巴胺水平的自身受体发挥作用。[13]D2Sh受体激动时抑制多巴胺释放，拮抗时增加多巴胺释放。[13]第三种D2（更长）的形式不同于270V被VVQ取代的规范序列。[14]

基因組

等位基因變異：

A-241G
C132T、G423A、T765C、C939T、C957T，以及G1101A[15]
Cys311Ser
-141C insertion/deletion[16]The polymorphisms have been investigated with respect to association with schizophrenia.[17]

Some researchers have previously associated the polymorphism Taq 1A (rs1800497) to the DRD2 gene. However, the polymorphism resides in exon 8 of the ANKK1 gene.[18]DRD2 TaqIA polymorphism has been reported to be associated with an increased risk for developing motor fluctuations but not hallucinations in Parkinson's disease.[19][20]

配體

大多数较老的抗精神病药如氯丙嗪或氟哌啶醇是多巴胺D₂受体的非选择性拮抗剂，最多仅对"D₂样家族"受体具有选择性，因此与D₂、D₃、D₄以及许多其他受体都可以结合，例如血清素和组胺受体，导致一系列副作用使得它们不适合科学研究。类似，用于治疗帕金森病的较旧的多巴胺激动剂例如溴隐亭和卡麦角林，对一种多巴胺受体的选择性较差，尽管这些药物中大多数确实能起到D₂激动剂的作用，但它们也会影响其他多巴胺受体，亚型也是。现今有几种选择性D₂配体 (生物化学)可以使用，并且随着进一步的研究，这个数字可能会增加。

受體致活劑

溴隱亭（Bromocriptine）：完全受體致活劑
Cabergoline（Caberl）
N,N-Propyldihydrexidine：D₁/D₅受體制活劑dihydrexidine的類似物，對節後神經元的D2R親和性比節前神經元的D₂自體受器高。
Piribedil：同時也是 D₃ 受體致活劑及腎上腺素α₂受體拮抗劑
Pramipexole：同時也是D₃、D₄受體致活劑
Quinelorane：affinity for D₂ > D₃
Quinpirole：同時也是D₃受體致活劑
Ropinirole：完全受體致活劑
Sumanirole：高選擇性完全受體致活劑
Talipexole：對D₂的親和性高於其他的多巴胺受體，但同時也是腎上腺素α₂受體制活劑及5-HT₃受體拮抗劑。

部分受體致活劑

Aplindore
阿立哌唑（Aripiprazole，在美國合法）[21]
Brexpiprazole/OPC-34712
Cariprazine
RP5063
GSK-789,472 – Also D₃ antagonist, with good selectivity over other receptors [22]
氯胺酮（Ketamine，同時也為NMDA受體拮抗劑）
LSD – in vitro, LSD was found to be a partial agonist and potentiates dopamine-mediated prolactin secretion in lactotrophs.[23]LSD is also a 5-HT_2A agonist.
莫达非尼（Modafinil）
Roxindole (only at the D₂ autoreceptors)
OSU-6162：亦為5-HT_2A部分受體致活劑，acts as "dopamine stabilizer"
Salvinorin A：亦為κ-鴉片類受體致活劑。

受體拮抗劑

Atypical antipsychotics
Desmethoxyfallypride
Domperidone – D₂ and D₃ antagonist; does not cross the blood-brain barrier
Eticlopride
Fallypride
Hydroxyzine (Vistaril, Atarax)
Itopride
L-741,626 – highly selective D₂ antagonist
C¹¹ Raclopride radiolabled – commonly employed in positron emission tomography studies[24]
Typical antipsychotics
SV 293[25]
Yohimbine

D₂sh selective (presynaptic autoreceptors)

氨磺必利 (low doses)
UH-232

異位調控因子

Homocysteine – 負向異位調控因子[26]
PAOPA[27]
SB-269,652 [28][29][30]

Functionally selective ligands

參見參考文獻[31]。

Protein–protein interactions

多巴胺受体 D₂ 已被证明与EPB41L1、[32]PPP1R9B[33] 和 NCS-1 相互作用。[34]

Receptor oligomers

The D₂ receptor forms receptor heterodimers in vivo (in living animals) with other G protein-coupled receptors; these include:[35]

D₁–D₂ dopamine receptor heteromer
D₂–adenosine A_2A
D₂–ghrelin receptor
D_2sh–TAAR1[note 1]

The D₂ receptor has been shown to form hetorodimers in vitro (and possibly in vivo) with DRD₃,[38]DRD₅,[39]and 5-HT_2A.[40]

註釋

D2sh–TAAR1 is a presynaptic heterodimer which involves the relocation of TAAR1 from the intracellular space to D2sh at the plasma membrane, increased D2sh agonist binding affinity, and signal transduction through the calcium–PKC–NFAT pathway and G-protein independent PKB–GSK3 pathway.[36][37]

參考文獻

.
.
.
GRCh38: Ensembl release 89: ENSG00000149295 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000032259 - Ensembl, May 2017
. National Center for Biotechnology Information, U.S. National Library of Medicine.
. National Center for Biotechnology Information, U.S. National Library of Medicine.
Madras BK. . Journal of the History of the Neurosciences. 2013, 22 (1): 62–78. PMID 23323533. doi:10.1080/0964704X.2012.678199.
Usiello A, Baik JH, Rougé-Pont F, Picetti R, Dierich A, LeMeur M, Piazza PV, Borrelli E. . Nature. Nov 2000, 408 (6809): 199–203. PMID 11089973. doi:10.1038/35041572.
Saab BJ, Georgiou J, Nath A, Lee FJ, Wang M, Michalon A, Liu F, Mansuy IM, Roder JC. . Neuron. Sep 2009, 63 (5): 643–56. PMID 19755107. doi:10.1016/j.neuron.2009.08.014.
Wiemerslage L, Schultz BJ, Ganguly A, Lee D. . Journal of Neurochemistry. Aug 2013, 126 (4): 529–40. PMID 23452092. doi:10.1111/jnc.12228.
. （原始内容存档于2010-03-07）.
Beaulieu JM, Gainetdinov RR. . Pharmacological Reviews. Mar 2011, 63 (1): 182–217. PMID 21303898. doi:10.1124/pr.110.002642.
UniProt P14416
Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, Gejman PV. . Human Molecular Genetics. Feb 2003, 12 (3): 205–16. PMID 12554675. doi:10.1093/hmg/ddg055.
Arinami T, Gao M, Hamaguchi H, Toru M. . Human Molecular Genetics. Apr 1997, 6 (4): 577–82. PMID 9097961. doi:10.1093/hmg/6.4.577.
Glatt SJ, Faraone SV, Tsuang MT. . American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. Jul 2004, 128B (1): 21–3. PMID 15211624. doi:10.1002/ajmg.b.30007.
Lucht M, Rosskopf D. . Science. Jul 2008, 321 (5886): 200; author reply 200. PMID 18621654. doi:10.1126/science.1155372.
Wang J, Liu ZL, Chen B. . Neurology. Jun 2001, 56 (12): 1757–9. PMID 11425949. doi:10.1212/WNL.56.12.1757.
Wang J, Zhao C, Chen B, Liu ZL. . Neuroscience Letters. Jan 2004, 355 (3): 193–6. PMID 14732464. doi:10.1016/j.neulet.2003.11.006.
. RxList.com. 2010-01-21 [2010-01-21]. （原始内容存档于2010-01-18）.
Holmes IP, Blunt RJ, Lorthioir OE, Blowers SM, Gribble A, Payne AH, Stansfield IG, Wood M, Woollard PM, Reavill C, Howes CM, Micheli F, Di Fabio R, Donati D, Terreni S, Hamprecht D, Arista L, Worby A, Watson SP. . Bioorganic & Medicinal Chemistry Letters. Mar 2010, 20 (6): 2013–6. PMID 20153647. doi:10.1016/j.bmcl.2010.01.090.
Giacomelli S, Palmery M, Romanelli L, Cheng CY, Silvestrini B. . Life Sciences. 1998, 63 (3): 215–22. PMID 9698051. doi:10.1016/S0024-3205(98)00262-8.
Wang GJ, Volkow ND, Thanos PK, Fowler JS. . Journal of Addictive Diseases. 2004, 23 (3): 39–53. PMID 15256343. doi:10.1300/J069v23n03_04.
Huang R, Griffin SA, Taylor M, Vangveravong S, Mach RH, Dillon GH, Luedtke RR. . Pharmacology. 2013, 92 (1–2): 84–9. PMID 23942137. doi:10.1159/000351971.
Agnati LF, Ferré S, Genedani S, Leo G, Guidolin D, Filaferro M, Carriba P, Casadó V, Lluis C, Franco R, Woods AS, Fuxe K. . Journal of Proteome Research. Nov 2006, 5 (11): 3077–83. PMID 17081059. doi:10.1021/pr0601382.
Beyaert MG, Daya RP, Dyck BA, Johnson RL, Mishra RK. . European Neuropsychopharmacology. Mar 2013, 23 (3): 253–62. PMID 22658400. doi:10.1016/j.euroneuro.2012.04.010.
Lane JR, Donthamsetti P, Shonberg J, Draper-Joyce CJ, Dentry S, Michino M, Shi L, López L, Scammells PJ, Capuano B, Sexton PM, Javitch JA, Christopoulos A. . Nature Chemical Biology. Sep 2014, 10 (9): 745–52. PMID 25108820. doi:10.1038/nchembio.1593.
Maggio R, Scarselli M, Capannolo M, Millan MJ. . European Neuropsychopharmacology. Sep 2015, 25 (9): 1470–9. PMID 25453482. doi:10.1016/j.euroneuro.2014.09.016.
Silvano E, Millan MJ, Mannoury la Cour C, Han Y, Duan L, Griffin SA, Luedtke RR, Aloisi G, Rossi M, Zazzeroni F, Javitch JA, Maggio R. . Molecular Pharmacology. Nov 2010, 78 (5): 925–34. PMC 2981362 . PMID 20702763. doi:10.1124/mol.110.065755.
Möller D, Kling RC, Skultety M, Leuner K, Hübner H, Gmeiner P. . Journal of Medicinal Chemistry. Jun 2014, 57 (11): 4861–75. PMID 24831693. doi:10.1021/jm5004039.
Binda AV, Kabbani N, Lin R, Levenson R. . Molecular Pharmacology. Sep 2002, 62 (3): 507–13. PMID 12181426. doi:10.1124/mol.62.3.507.
Smith FD, Oxford GS, Milgram SL. . The Journal of Biological Chemistry. Jul 1999, 274 (28): 19894–900. PMID 10391935. doi:10.1074/jbc.274.28.19894.
Kabbani N, Negyessy L, Lin R, Goldman-Rakic P, Levenson R. . The Journal of Neuroscience. Oct 2002, 22 (19): 8476–86. PMID 12351722.
Beaulieu JM, Espinoza S, Gainetdinov RR. . British Journal of Pharmacology. Jan 2015, 172 (1): 1–23. PMC 4280963 . PMID 25671228. doi:10.1111/bph.12906.
Grandy DK, Miller GM, Li JX. . Drug Alcohol Depend. February 2016, 159: 9–16. PMID 26644139. doi:10.1016/j.drugalcdep.2015.11.014. This original observation of TAAR1 and DA D2R interaction has subsequently been confirmed and expanded upon with observations that both receptors can heterodimerize with each other under certain conditions ... Additional DA D2R/TAAR1 interactions with functional consequences are revealed by the results of experiments demonstrating that in addition to the cAMP/PKA pathway (Panas et al., 2012) stimulation of TAAR1-mediated signaling is linked to activation of the Ca++/PKC/NFAT pathway (Panas et al.,2012) and the DA D2R-coupled, G protein-independent AKT/GSK3 signaling pathway (Espinoza et al., 2015; Harmeier et al., 2015), such that concurrent TAAR1 and DA DR2R activation could result in diminished signaling in one pathway (e.g. cAMP/PKA) but retention of signaling through another (e.g., Ca++/PKC/NFA)
Harmeier A, Obermueller S, Meyer CA, Revel FG, Buchy D, Chaboz S, Dernick G, Wettstein JG, Iglesias A, Rolink A, Bettler B, Hoener MC. . Eur Neuropsychopharmacol. 2015, 25 (11): 2049–61. PMID 26372541. doi:10.1016/j.euroneuro.2015.08.011. Interaction of TAAR1 with D2R altered the subcellular localization of TAAR1 and increased D2R agonist binding affinity.
Maggio R, Millan MJ. . Current Opinion in Pharmacology. Feb 2010, 10 (1): 100–7. PMID 19896900. doi:10.1016/j.coph.2009.10.001.
Hasbi A, O'Dowd BF, George SR. . Current Opinion in Pharmacology. Feb 2010, 10 (1): 93–9. PMC 2818238 . PMID 19897420. doi:10.1016/j.coph.2009.09.011.
Albizu L, Holloway T, González-Maeso J, Sealfon SC. . Neuropharmacology. Sep 2011, 61 (4): 770–7. PMC 3556730 . PMID 21645528. doi:10.1016/j.neuropharm.2011.05.023.

外部連結

醫學主題詞表（MeSH）：Receptors,+Dopamine+D2
Pappas, Stephanie. . Imaginova Corp. LiveScience. [20 January 2011].

多巴胺受體D2引用了美国国家医学图书馆提供的資料，这些資料属于公共领域。

Template:Dopaminergics

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[38] D2sh–TAAR1 is a presynaptic heterodimer which involves the relocation of TAAR1 from the intracellular space to D2sh at the plasma membrane, increased D2sh agonist binding affinity, and signal transduction through the calcium–PKC–NFAT pathway and G-protein independent PKB–GSK3 pathway.[36][37]

[1] .

[2] .

[3] .

[refGRCh38Ensembl-4] GRCh38: Ensembl release 89: ENSG00000149295 - Ensembl, May 2017

[refGRCm38Ensembl-5] GRCm38: Ensembl release 89: ENSMUSG00000032259 - Ensembl, May 2017

[6] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[7] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[8] Madras BK. . Journal of the History of the Neurosciences. 2013, 22 (1): 62–78. PMID 23323533. doi:10.1080/0964704X.2012.678199.

[pmid11089973-9] Usiello A, Baik JH, Rougé-Pont F, Picetti R, Dierich A, LeMeur M, Piazza PV, Borrelli E. . Nature. Nov 2000, 408 (6809): 199–203. PMID 11089973. doi:10.1038/35041572.

[pmid19755107-10] Saab BJ, Georgiou J, Nath A, Lee FJ, Wang M, Michalon A, Liu F, Mansuy IM, Roder JC. . Neuron. Sep 2009, 63 (5): 643–56. PMID 19755107. doi:10.1016/j.neuron.2009.08.014.

[pmid23452092-11] Wiemerslage L, Schultz BJ, Ganguly A, Lee D. . Journal of Neurochemistry. Aug 2013, 126 (4): 529–40. PMID 23452092. doi:10.1111/jnc.12228.

[entrez-12] . （原始内容存档于2010-03-07）.

[D2_Long_and_short-13] Beaulieu JM, Gainetdinov RR. . Pharmacological Reviews. Mar 2011, 63 (1): 182–217. PMID 21303898. doi:10.1124/pr.110.002642.

[uniprot-14] UniProt P14416

[pmid12554675-15] Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, Gejman PV. . Human Molecular Genetics. Feb 2003, 12 (3): 205–16. PMID 12554675. doi:10.1093/hmg/ddg055.

[pmid9097961-16] Arinami T, Gao M, Hamaguchi H, Toru M. . Human Molecular Genetics. Apr 1997, 6 (4): 577–82. PMID 9097961. doi:10.1093/hmg/6.4.577.

[pmid15211624-17] Glatt SJ, Faraone SV, Tsuang MT. . American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. Jul 2004, 128B (1): 21–3. PMID 15211624. doi:10.1002/ajmg.b.30007.

[pmid18621654-18] Lucht M, Rosskopf D. . Science. Jul 2008, 321 (5886): 200; author reply 200. PMID 18621654. doi:10.1126/science.1155372.

[pmid11425949-19] Wang J, Liu ZL, Chen B. . Neurology. Jun 2001, 56 (12): 1757–9. PMID 11425949. doi:10.1212/WNL.56.12.1757.

[Wang_J,_Zhao_c,_Chen_B,_Liu_Z._2004-20] Wang J, Zhao C, Chen B, Liu ZL. . Neuroscience Letters. Jan 2004, 355 (3): 193–6. PMID 14732464. doi:10.1016/j.neulet.2003.11.006.

[Rxlist_-_Abilify-21] . RxList.com. 2010-01-21 [2010-01-21]. （原始内容存档于2010-01-18）.

[pmid20153647-22] Holmes IP, Blunt RJ, Lorthioir OE, Blowers SM, Gribble A, Payne AH, Stansfield IG, Wood M, Woollard PM, Reavill C, Howes CM, Micheli F, Di Fabio R, Donati D, Terreni S, Hamprecht D, Arista L, Worby A, Watson SP. . Bioorganic & Medicinal Chemistry Letters. Mar 2010, 20 (6): 2013–6. PMID 20153647. doi:10.1016/j.bmcl.2010.01.090.

[pmid9698051-23] Giacomelli S, Palmery M, Romanelli L, Cheng CY, Silvestrini B. . Life Sciences. 1998, 63 (3): 215–22. PMID 9698051. doi:10.1016/S0024-3205(98)00262-8.

[pmid15256343-24] Wang GJ, Volkow ND, Thanos PK, Fowler JS. . Journal of Addictive Diseases. 2004, 23 (3): 39–53. PMID 15256343. doi:10.1300/J069v23n03_04.

[25] Huang R, Griffin SA, Taylor M, Vangveravong S, Mach RH, Dillon GH, Luedtke RR. . Pharmacology. 2013, 92 (1–2): 84–9. PMID 23942137. doi:10.1159/000351971.

[26] Agnati LF, Ferré S, Genedani S, Leo G, Guidolin D, Filaferro M, Carriba P, Casadó V, Lluis C, Franco R, Woods AS, Fuxe K. . Journal of Proteome Research. Nov 2006, 5 (11): 3077–83. PMID 17081059. doi:10.1021/pr0601382.

[27] Beyaert MG, Daya RP, Dyck BA, Johnson RL, Mishra RK. . European Neuropsychopharmacology. Mar 2013, 23 (3): 253–62. PMID 22658400. doi:10.1016/j.euroneuro.2012.04.010.

[pmid25108820-28] Lane JR, Donthamsetti P, Shonberg J, Draper-Joyce CJ, Dentry S, Michino M, Shi L, López L, Scammells PJ, Capuano B, Sexton PM, Javitch JA, Christopoulos A. . Nature Chemical Biology. Sep 2014, 10 (9): 745–52. PMID 25108820. doi:10.1038/nchembio.1593.

[pmid25453482-29] Maggio R, Scarselli M, Capannolo M, Millan MJ. . European Neuropsychopharmacology. Sep 2015, 25 (9): 1470–9. PMID 25453482. doi:10.1016/j.euroneuro.2014.09.016.

[30] Silvano E, Millan MJ, Mannoury la Cour C, Han Y, Duan L, Griffin SA, Luedtke RR, Aloisi G, Rossi M, Zazzeroni F, Javitch JA, Maggio R. . Molecular Pharmacology. Nov 2010, 78 (5): 925–34. PMC 2981362 . PMID 20702763. doi:10.1124/mol.110.065755.

[pmid24831693-31] Möller D, Kling RC, Skultety M, Leuner K, Hübner H, Gmeiner P. . Journal of Medicinal Chemistry. Jun 2014, 57 (11): 4861–75. PMID 24831693. doi:10.1021/jm5004039.

[pmid12181426-32] Binda AV, Kabbani N, Lin R, Levenson R. . Molecular Pharmacology. Sep 2002, 62 (3): 507–13. PMID 12181426. doi:10.1124/mol.62.3.507.

[pmid10391935-33] Smith FD, Oxford GS, Milgram SL. . The Journal of Biological Chemistry. Jul 1999, 274 (28): 19894–900. PMID 10391935. doi:10.1074/jbc.274.28.19894.

[pmid12351722-34] Kabbani N, Negyessy L, Lin R, Goldman-Rakic P, Levenson R. . The Journal of Neuroscience. Oct 2002, 22 (19): 8476–86. PMID 12351722.

[DA_receptor_heterodimers-35] Beaulieu JM, Espinoza S, Gainetdinov RR. . British Journal of Pharmacology. Jan 2015, 172 (1): 1–23. PMC 4280963 . PMID 25671228. doi:10.1111/bph.12906.

[Miller+Grandy_2016-36] Grandy DK, Miller GM, Li JX. . Drug Alcohol Depend. February 2016, 159: 9–16. PMID 26644139. doi:10.1016/j.drugalcdep.2015.11.014. This original observation of TAAR1 and DA D2R interaction has subsequently been confirmed and expanded upon with observations that both receptors can heterodimerize with each other under certain conditions ... Additional DA D2R/TAAR1 interactions with functional consequences are revealed by the results of experiments demonstrating that in addition to the cAMP/PKA pathway (Panas et al., 2012) stimulation of TAAR1-mediated signaling is linked to activation of the Ca++/PKC/NFAT pathway (Panas et al.,2012) and the DA D2R-coupled, G protein-independent AKT/GSK3 signaling pathway (Espinoza et al., 2015; Harmeier et al., 2015), such that concurrent TAAR1 and DA DR2R activation could result in diminished signaling in one pathway (e.g. cAMP/PKA) but retention of signaling through another (e.g., Ca++/PKC/NFA)

[TAAR1-D2sh-37] Harmeier A, Obermueller S, Meyer CA, Revel FG, Buchy D, Chaboz S, Dernick G, Wettstein JG, Iglesias A, Rolink A, Bettler B, Hoener MC. . Eur Neuropsychopharmacol. 2015, 25 (11): 2049–61. PMID 26372541. doi:10.1016/j.euroneuro.2015.08.011. Interaction of TAAR1 with D2R altered the subcellular localization of TAAR1 and increased D2R agonist binding affinity.

[39] Maggio R, Millan MJ. . Current Opinion in Pharmacology. Feb 2010, 10 (1): 100–7. PMID 19896900. doi:10.1016/j.coph.2009.10.001.

[40] Hasbi A, O'Dowd BF, George SR. . Current Opinion in Pharmacology. Feb 2010, 10 (1): 93–9. PMC 2818238 . PMID 19897420. doi:10.1016/j.coph.2009.09.011.

[41] Albizu L, Holloway T, González-Maeso J, Sealfon SC. . Neuropharmacology. Sep 2011, 61 (4): 770–7. PMC 3556730 . PMID 21645528. doi:10.1016/j.neuropharm.2011.05.023.