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D1–D2 dopamine receptor heteromer

April 14, 2024

The D1–D2 dopamine receptor heteromer is a receptor heteromer consisting of D1 and D2 protomers.

Dopamine receptor D1
Identifiers
SymbolDRD1
NCBI gene1812
HGNC3020
OMIM126449
RefSeqNP_000785
UniProtP21728
Other data
LocusChr. 5 q35.2
Search for
StructuresSwiss-model
DomainsInterPro
Dopamine receptor D2
Identifiers
SymbolDRD2
NCBI gene1813
HGNC3023
OMIM126450
RefSeqNP_000786
UniProtP14416
Other data
LocusChr. 11 q22
Search for
StructuresSwiss-model
DomainsInterPro

Structure edit

D1 and D2 receptors interact primarily through discrete amino acids in the cytoplasmic regions of each receptor, with no involvement of transmembrane parts. The intracellular loop 3 of the D2 receptor contains two adjacent arginine residues, while the carboxyl tail of the D1 receptor possesses two adjacent glutamic acid residues. The two receptors can form a heteromer complex via a salt bridge between the guanidine moiety and the carboxylic group.[1]

Signal transduction edit

The signalling of the D1–D2 receptor heteromer is distinct from that of the parent receptor monomers. It comprises Gq/11 coupling, phospholipase C activation, intracellular calcium release from inositol trisphosphate receptor-sensitive stores, CaMKII activation[2] and BDNF production.[3] In comparison, signalling of the homologous D5–D2 receptor heteromer involves the influx of extracellular calcium.[4]

Physiology edit

The D1–D2 receptor is upregulated in individuals with major depression, and especially the ratio D1–D2 to D1 receptor is markedly shifted towards the heteromer. Counteracting this upregulation decreases depressive symptoms. Disruption of the heteromer can be achieved either directly by ligands interacting with the cytoplasmic interface, less directly by ligands that target the extracellular binding site, or indirectly as a downstream effect of classical antidepressant treatment.[5] One study found negative results regarding a shift from Gs/a coupling to Gq/11 signaling; so such dynamics could be mediated by cAMP-dependent cascades rather from phospholipase C regulation.[6]

Chronic THC increased the number of D1-D2 heteromer-expressing neurons, and the number of heteromers within individual neurons in adult monkey striatum.[7]

Ligands edit

References edit

  1. ^ O'Dowd BF, Ji X, Nguyen T, George SR (January 2012). "Two amino acids in each of D1 and D2 dopamine receptor cytoplasmic regions are involved in D1-D2 heteromer formation". Biochemical and Biophysical Research Communications. 417 (1): 23–8. doi:10.1016/j.bbrc.2011.11.027. PMC 4243167. PMID 22100647.
  2. ^ Ng J, Rashid AJ, So CH, O'Dowd BF, George SR (January 2010). "Activation of calcium/calmodulin-dependent protein kinase IIalpha in the striatum by the heteromeric D1-D2 dopamine receptor complex". Neuroscience. 165 (2): 535–41. doi:10.1016/j.neuroscience.2009.10.017. PMC 2814448. PMID 19837142.
  3. ^ Hasbi A, Fan T, Alijaniaram M, Nguyen T, Perreault ML, O'Dowd BF, George SR (December 2009). "Calcium signaling cascade links dopamine D1-D2 receptor heteromer to striatal BDNF production and neuronal growth". Proceedings of the National Academy of Sciences of the United States of America. 106 (50): 21377–82. Bibcode:2009PNAS..10621377H. doi:10.1073/pnas.0903676106. PMC 2795506. PMID 19948956.
  4. ^ Hasbi A, O'Dowd BF, George SR (February 2010). "Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms". Current Opinion in Pharmacology. 10 (1): 93–9. doi:10.1016/j.coph.2009.09.011. PMC 2818238. PMID 19897420.
  5. ^ Pei L, Li S, Wang M, Diwan M, Anisman H, Fletcher PJ, et al. (December 2010). "Uncoupling the dopamine D1-D2 receptor complex exerts antidepressant-like effects". Nature Medicine. 16 (12): 1393–5. doi:10.1038/nm.2263. PMID 21113156. S2CID 205387382.
  6. ^ Frederick AL, Yano H, Trifilieff P, Vishwasrao HD, Biezonski D, Mészáros J, et al. (November 2015). "Evidence against dopamine D1/D2 receptor heteromers". Molecular Psychiatry. 20 (11): 1373–85. doi:10.1038/mp.2014.166. PMC 4492915. PMID 25560761.
  7. ^ Hasbi A, Madras BK, Bergman J, Kohut S, Lin Z, Withey SL, George SR (January 2020). "Δ-Tetrahydrocannabinol Increases Dopamine D1-D2 Receptor Heteromer and Elicits Phenotypic Reprogramming in Adult Primate Striatal Neurons". iScience. 23 (1): 100794. Bibcode:2020iSci...23j0794H. doi:10.1016/j.isci.2019.100794. PMC 6971351. PMID 31972514.
  8. ^ Rashid AJ, So CH, Kong MM, Furtak T, El-Ghundi M, Cheng R, et al. (January 2007). "D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum". Proceedings of the National Academy of Sciences of the United States of America. 104 (2): 654–9. Bibcode:2007PNAS..104..654R. doi:10.1073/pnas.0604049104. PMC 1766439. PMID 17194762.

Further reading edit

  • Perreault ML, Fan T, Alijaniaram M, O'Dowd BF, George SR (2012). "Dopamine D1-D2 receptor heteromer in dual phenotype GABA/glutamate-coexpressing striatal medium spiny neurons: regulation of BDNF, GAD67 and VGLUT1/2". PLOS ONE. 7 (3): e33348. Bibcode:2012PLoSO...733348P. doi:10.1371/journal.pone.0033348. PMC 3299775. PMID 22428025.
  • Perreault ML, Hasbi A, O'Dowd BF, George SR (2011). "The dopamine d1-d2 receptor heteromer in striatal medium spiny neurons: evidence for a third distinct neuronal pathway in Basal Ganglia". Frontiers in Neuroanatomy. 5: 31. doi:10.3389/fnana.2011.00031. PMC 3130461. PMID 21747759.
  • Perreault ML, Hasbi A, Alijaniaram M, Fan T, Varghese G, Fletcher PJ, et al. (November 2010). "The dopamine D1-D2 receptor heteromer localizes in dynorphin/enkephalin neurons: increased high affinity state following amphetamine and in schizophrenia". The Journal of Biological Chemistry. 285 (47): 36625–34. doi:10.1074/jbc.M110.159954. PMC 2978591. PMID 20864528.
  • Hasbi A, O'Dowd BF, George SR (June 2011). "Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance". Molecular Brain. 4: 26. doi:10.1186/1756-6606-4-26. PMC 3138392. PMID 21663703.
  • George SR, O'Dowd BF (November 2007). "A novel dopamine receptor signaling unit in brain: heterooligomers of D1 and D2 dopamine receptors". TheScientificWorldJournal. 7: 58–63. doi:10.1100/tsw.2007.223. PMC 5900862. PMID 17982577.
  • So CH, Verma V, O'Dowd BF, George SR (August 2007). "Desensitization of the dopamine D1 and D2 receptor hetero-oligomer mediated calcium signal by agonist occupancy of either receptor". Molecular Pharmacology. 72 (2): 450–62. doi:10.1124/mol.107.034884. PMID 17519357. S2CID 12345381.
  • So CH, Varghese G, Curley KJ, Kong MM, Alijaniaram M, Ji X, et al. (September 2005). "D1 and D2 dopamine receptors form heterooligomers and cointernalize after selective activation of either receptor". Molecular Pharmacology. 68 (3): 568–78. doi:10.1124/mol.105.012229. PMID 15923381. S2CID 2565690.
  • Verma V, Hasbi A, O'Dowd BF, George SR (November 2010). "Dopamine D1-D2 receptor Heteromer-mediated calcium release is desensitized by D1 receptor occupancy with or without signal activation: dual functional regulation by G protein-coupled receptor kinase 2". The Journal of Biological Chemistry. 285 (45): 35092–103. doi:10.1074/jbc.M109.088625. PMC 2966123. PMID 20807772.
  • O'Dowd BF, Ji X, Alijaniaram M, Nguyen T, George SR (May 2011). "Separation and reformation of cell surface dopamine receptor oligomers visualized in cells". European Journal of Pharmacology. 658 (2–3): 74–83. doi:10.1016/j.ejphar.2011.02.030. PMID 21371461.
  • Dziedzicka-Wasylewska M, Faron-Górecka A, Andrecka J, Polit A, Kuśmider M, Wasylewski Z (July 2006). "Fluorescence studies reveal heterodimerization of dopamine D1 and D2 receptors in the plasma membrane". Biochemistry. 45 (29): 8751–9. doi:10.1021/bi060702m. PMID 16846218.
  • Dziedzicka-Wasylewska M, Faron-Górecka A, Górecki A, Kuśemider M (2008). "Mechanism of action of clozapine in the context of dopamine D1-D2 receptor hetero-dimerization--a working hypothesis". Pharmacological Reports. 60 (5): 581–7. PMID 19066405.
  • Grymek K, Łukasiewicz S, Faron-Góreckaa A, Tworzydlo M, Polit A, Dziedzicka-Wasylewska M (2009). "Role of silent polymorphisms within the dopamine D1 receptor associated with schizophrenia on D1-D2 receptor hetero-dimerization". Pharmacological Reports. 61 (6): 1024–33. doi:10.1016/s1734-1140(09)70164-1. PMID 20081237. S2CID 4734776.
  • Błasiak E, Łukasiewicz S, Szafran-Pilch K, Dziedzicka-Wasylewska M (April 2017). "Genetic variants of dopamine D2 receptor impact heterodimerization with dopamine D1 receptor". Pharmacological Reports. 69 (2): 235–241. doi:10.1016/j.pharep.2016.10.016. PMID 28119185. S2CID 11334015.

April 14, 2024
dopamine, receptor, heteromer, dopamine, receptor, heteromer, receptor, heteromer, consisting, protomers, dopamine, receptor, d1identifierssymboldrd1ncbi, gene1812hgnc3020omim126449refseqnp, 000785uniprotp21728other, datalocuschr, 2search, forstructuresswiss, . The D1 D2 dopamine receptor heteromer is a receptor heteromer consisting of D1 and D2 protomers Dopamine receptor D1IdentifiersSymbolDRD1NCBI gene1812HGNC3020OMIM126449RefSeqNP 000785UniProtP21728Other dataLocusChr 5 q35 2Search forStructuresSwiss modelDomainsInterProDopamine receptor D2IdentifiersSymbolDRD2NCBI gene1813HGNC3023OMIM126450RefSeqNP 000786UniProtP14416Other dataLocusChr 11 q22Search forStructuresSwiss modelDomainsInterPro Contents 1 Structure 2 Signal transduction 3 Physiology 4 Ligands 5 References 6 Further readingStructure editD1 and D2 receptors interact primarily through discrete amino acids in the cytoplasmic regions of each receptor with no involvement of transmembrane parts The intracellular loop 3 of the D2 receptor contains two adjacent arginine residues while the carboxyl tail of the D1 receptor possesses two adjacent glutamic acid residues The two receptors can form a heteromer complex via a salt bridge between the guanidine moiety and the carboxylic group 1 Signal transduction editThe signalling of the D1 D2 receptor heteromer is distinct from that of the parent receptor monomers It comprises Gq 11 coupling phospholipase C activation intracellular calcium release from inositol trisphosphate receptor sensitive stores CaMKII activation 2 and BDNF production 3 In comparison signalling of the homologous D5 D2 receptor heteromer involves the influx of extracellular calcium 4 Physiology editThe D1 D2 receptor is upregulated in individuals with major depression and especially the ratio D1 D2 to D1 receptor is markedly shifted towards the heteromer Counteracting this upregulation decreases depressive symptoms Disruption of the heteromer can be achieved either directly by ligands interacting with the cytoplasmic interface less directly by ligands that target the extracellular binding site or indirectly as a downstream effect of classical antidepressant treatment 5 One study found negative results regarding a shift from Gs a coupling to Gq 11 signaling so such dynamics could be mediated by cAMP dependent cascades rather from phospholipase C regulation 6 Chronic THC increased the number of D1 D2 heteromer expressing neurons and the number of heteromers within individual neurons in adult monkey striatum 7 Ligands editSKF 83 959 8 References edit O Dowd BF Ji X Nguyen T George SR January 2012 Two amino acids in each of D1 and D2 dopamine receptor cytoplasmic regions are involved in D1 D2 heteromer formation Biochemical and Biophysical Research Communications 417 1 23 8 doi 10 1016 j bbrc 2011 11 027 PMC 4243167 PMID 22100647 Ng J Rashid AJ So CH O Dowd BF George SR January 2010 Activation of calcium calmodulin dependent protein kinase IIalpha in the striatum by the heteromeric D1 D2 dopamine receptor complex Neuroscience 165 2 535 41 doi 10 1016 j neuroscience 2009 10 017 PMC 2814448 PMID 19837142 Hasbi A Fan T Alijaniaram M Nguyen T Perreault ML O Dowd BF George SR December 2009 Calcium signaling cascade links dopamine D1 D2 receptor heteromer to striatal BDNF production and neuronal growth Proceedings of the National Academy of Sciences of the United States of America 106 50 21377 82 Bibcode 2009PNAS 10621377H doi 10 1073 pnas 0903676106 PMC 2795506 PMID 19948956 Hasbi A O Dowd BF George SR February 2010 Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms Current Opinion in Pharmacology 10 1 93 9 doi 10 1016 j coph 2009 09 011 PMC 2818238 PMID 19897420 Pei L Li S Wang M Diwan M Anisman H Fletcher PJ et al December 2010 Uncoupling the dopamine D1 D2 receptor complex exerts antidepressant like effects Nature Medicine 16 12 1393 5 doi 10 1038 nm 2263 PMID 21113156 S2CID 205387382 Frederick AL Yano H Trifilieff P Vishwasrao HD Biezonski D Meszaros J et al November 2015 Evidence against dopamine D1 D2 receptor heteromers Molecular Psychiatry 20 11 1373 85 doi 10 1038 mp 2014 166 PMC 4492915 PMID 25560761 Hasbi A Madras BK Bergman J Kohut S Lin Z Withey SL George SR January 2020 D Tetrahydrocannabinol Increases Dopamine D1 D2 Receptor Heteromer and Elicits Phenotypic Reprogramming in Adult Primate Striatal Neurons iScience 23 1 100794 Bibcode 2020iSci 23j0794H doi 10 1016 j isci 2019 100794 PMC 6971351 PMID 31972514 Rashid AJ So CH Kong MM Furtak T El Ghundi M Cheng R et al January 2007 D1 D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq 11 in the striatum Proceedings of the National Academy of Sciences of the United States of America 104 2 654 9 Bibcode 2007PNAS 104 654R doi 10 1073 pnas 0604049104 PMC 1766439 PMID 17194762 Further reading editPerreault ML Fan T Alijaniaram M O Dowd BF George SR 2012 Dopamine D1 D2 receptor heteromer in dual phenotype GABA glutamate coexpressing striatal medium spiny neurons regulation of BDNF GAD67 and VGLUT1 2 PLOS ONE 7 3 e33348 Bibcode 2012PLoSO 733348P doi 10 1371 journal pone 0033348 PMC 3299775 PMID 22428025 Perreault ML Hasbi A O Dowd BF George SR 2011 The dopamine d1 d2 receptor heteromer in striatal medium spiny neurons evidence for a third distinct neuronal pathway in Basal Ganglia Frontiers in Neuroanatomy 5 31 doi 10 3389 fnana 2011 00031 PMC 3130461 PMID 21747759 Perreault ML Hasbi A Alijaniaram M Fan T Varghese G Fletcher PJ et al November 2010 The dopamine D1 D2 receptor heteromer localizes in dynorphin enkephalin neurons increased high affinity state following amphetamine and in schizophrenia The Journal of Biological Chemistry 285 47 36625 34 doi 10 1074 jbc M110 159954 PMC 2978591 PMID 20864528 Hasbi A O Dowd BF George SR June 2011 Dopamine D1 D2 receptor heteromer signaling pathway in the brain emerging physiological relevance Molecular Brain 4 26 doi 10 1186 1756 6606 4 26 PMC 3138392 PMID 21663703 George SR O Dowd BF November 2007 A novel dopamine receptor signaling unit in brain heterooligomers of D1 and D2 dopamine receptors TheScientificWorldJournal 7 58 63 doi 10 1100 tsw 2007 223 PMC 5900862 PMID 17982577 So CH Verma V O Dowd BF George SR August 2007 Desensitization of the dopamine D1 and D2 receptor hetero oligomer mediated calcium signal by agonist occupancy of either receptor Molecular Pharmacology 72 2 450 62 doi 10 1124 mol 107 034884 PMID 17519357 S2CID 12345381 So CH Varghese G Curley KJ Kong MM Alijaniaram M Ji X et al September 2005 D1 and D2 dopamine receptors form heterooligomers and cointernalize after selective activation of either receptor Molecular Pharmacology 68 3 568 78 doi 10 1124 mol 105 012229 PMID 15923381 S2CID 2565690 Verma V Hasbi A O Dowd BF George SR November 2010 Dopamine D1 D2 receptor Heteromer mediated calcium release is desensitized by D1 receptor occupancy with or without signal activation dual functional regulation by G protein coupled receptor kinase 2 The Journal of Biological Chemistry 285 45 35092 103 doi 10 1074 jbc M109 088625 PMC 2966123 PMID 20807772 O Dowd BF Ji X Alijaniaram M Nguyen T George SR May 2011 Separation and reformation of cell surface dopamine receptor oligomers visualized in cells European Journal of Pharmacology 658 2 3 74 83 doi 10 1016 j ejphar 2011 02 030 PMID 21371461 Dziedzicka Wasylewska M Faron Gorecka A Andrecka J Polit A Kusmider M Wasylewski Z July 2006 Fluorescence studies reveal heterodimerization of dopamine D1 and D2 receptors in the plasma membrane Biochemistry 45 29 8751 9 doi 10 1021 bi060702m PMID 16846218 Dziedzicka Wasylewska M Faron Gorecka A Gorecki A Kusemider M 2008 Mechanism of action of clozapine in the context of dopamine D1 D2 receptor hetero dimerization a working hypothesis Pharmacological Reports 60 5 581 7 PMID 19066405 Grymek K Lukasiewicz S Faron Goreckaa A Tworzydlo M Polit A Dziedzicka Wasylewska M 2009 Role of silent polymorphisms within the dopamine D1 receptor associated with schizophrenia on D1 D2 receptor hetero dimerization Pharmacological Reports 61 6 1024 33 doi 10 1016 s1734 1140 09 70164 1 PMID 20081237 S2CID 4734776 Blasiak E Lukasiewicz S Szafran Pilch K Dziedzicka Wasylewska M April 2017 Genetic variants of dopamine D2 receptor impact heterodimerization with dopamine D1 receptor Pharmacological Reports 69 2 235 241 doi 10 1016 j pharep 2016 10 016 PMID 28119185 S2CID 11334015 Retrieved from https en wikipedia org w index php title D1 D2 dopamine receptor heteromer amp oldid 1171404125, wikipedia, wiki, book, books, library,

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