Are dopamine D2 receptors out of control in psychosis?

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volumn 46, Issue , 2013, Pages 146-152

  Seeman, Philip ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

Caudate nucleus; Dopamine supersensitivity; Psychosis; Putamen; Schizophrenia; Striatum

Indexed keywords

AMPHETAMINE; CLATHRIN; CYCLIC AMP DEPENDENT PROTEIN KINASE; DIMER; DOPAMINE; DOPAMINE 2 RECEPTOR; G PROTEIN COUPLED RECEPTOR KINASE; GUANOSINE TRIPHOSPHATASE; GUANOSINE TRIPHOSPHATE; HALOPERIDOL; METHYLPHENIDATE; PROTEIN KINASE C; RADIOLIGAND; RETINA S ANTIGEN;

DEPHOSPHORYLATION; DISEASE MODEL; DOPAMINE RELEASE; DRUG SENSITIVITY; ENZYME PHOSPHORYLATION; ENZYME REGULATION; EXPERIMENTAL ANIMAL; HUMAN; IN VIVO STUDY; NONHUMAN; PROTEIN LOCALIZATION; PSYCHOSIS; RECEPTOR BINDING; REVIEW; SCHIZOPHRENIA;

CAUDATE NUCLEUS; DOPAMINE SUPERSENSITIVITY; PSYCHOSIS; PUTAMEN; SCHIZOPHRENIA; STRIATUM;

ANIMALS; DOPAMINE; DOPAMINE ANTAGONISTS; HUMANS; PROTEIN BINDING; PSYCHOTIC DISORDERS; RECEPTORS, DOPAMINE D2; SCHIZOPHRENIA;

EID: 84881534779     PISSN: 02785846     EISSN: 18784216     Source Type: Journal    
DOI: 10.1016/j.pnpbp.2013.07.006     Document Type: Review

References (107)

1. Abi-Dargham A., Rodenhiser J., Printz D., Zea-Ponce Y., Gil R., Kegeles L.S., et al. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci U S A 2000, 97:8104-8109.
2. Amar S., Shaltiel G., Mann L., Shamir A., Dean B., Scarr E., et al. Possible involvement of post-dopamine D2 receptor signalling components in the pathophysiology of schizophrenia. Int J Neuropsychopharmacol 2008, 11:197-205.
3. Bai J., He F., Novikova S.I., Undie A.S., Dracheva S., Haroutunian V., et al. Abnormalities in the dopamine system in schizophrenia may lie in altered levels of dopamine receptor-interacting proteins. Biol Psychiatry 2004, 56:427-440.
4. Beaulieu J.M., Gainetdinov R.R. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 2011, 63:182-217.
5. (2+) connection in dopamine signaling. Trends Pharmacol Sci 2003, 24:486-492.
6. Binda A.V., Kabbani N., Lin R., Levenson R. D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N. Mol Pharmacol 2002, 62:507-513.
7. Binda A.V., Kabbani N., Levenson R. Regulation of dense core vesicle release from PC12 cells by interaction between the D2 dopamine receptor and calcium-dependent activator protein for secretion (CAPS). Biochem Pharmacol 2005, 69:1451-1461.
8. Bishop C., Rankine D.M., Talbott J.H. The nucleotides in normal human blood. J Biol Chem 1959, 234:1233-1237.
9. Bofill-Cardona E., Kudlacek O., Yang Q., Ahorn H., Freissmuth M., Nanoff C. Binding of calmodulin to the D2-dopamine receptor reduces receptor signaling by arresting the G protein activation switch. J Biol Chem 2000, 275:32672-32680.
10. Broadbelt K., Jones L.B. Evidence of altered calmodulin immunoreactivity in areas 9 and 32 of schizophrenic prefrontal cortex. J Psychiatr Res 2008, 42:612-621.
11. Bychkov E.R., Ahmed M.R., Gurevich V.V., Benovic J.L., Gurevich E.V. Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder. Neurobiol Dis 2011, 44:248-258.
12. Carroll L.S., Williams N.M., Moskvina V., Russell E., Norton N., Williams H.J., et al. Evidence for rare and common genetic risk variants for schizophrenia at protein kinase C, alpha. Mol Psychiatry 2010, 15(11):1101-1111.
13. Cherfils J., Mahel Zeghouf M. Regulation of small GTPases by GEFs, GAPs and GDIs. Physiol Rev 2013, 93:269-309.
14. Cho D., Zheng M., Min C., Ma L., Kurose H., Park J.H., et al. Agonist-induced endocytosis and receptor phosphorylation mediate resensitization of dopamine D(2) receptors. Mol Endocrinol 2010, 24(3):574-586.
15. Chouinard G. Severe cases of neuroleptic-induced supersensitivity psychosis. Diagnostic criteria for the disorder and its treatment. Schizophr Res 1991, 5:21-33.
16. Chouinard G., Vainer J.L., Bélanger M.C., Turnier L., Beaudry P., Roy J.Y., et al. Risperidone and clozapine in the treatment of drug-resistant schizophrenia and neuroleptic-induced supersensitivity psychosis. Prog Neuropsychopharmacol Biol Psychiatry 1994, 18:1129-1141.
17. Clinton S.M., Ibrahim H.M., Frey K.A., Davis K.L., Haroutunian V., Meador-Woodruff J.H. Dopaminergic abnormalities in select thalamic nuclei in schizophrenia: involvement of the intracellular signal integrating proteins calcyon and spinophilin. Am J Psychiatry 2005, 162:1859-1871.
18. Corripio I., Pérez V., Catafau A.M., Mena E., Carrió I., Alvarez E. Striatal D2 receptor binding as a marker of prognosis and outcome in untreated first-episode psychosis. Neuroimage 2006, 29:662-666. [Erratum in: Neuroimage 2006, Sept 32, 1483].
19. Corripio I., Escartí M.J., Portella M.J., Pérez V., Grasa E., Sauras R.B., et al. Density of striatal D2 receptors in untreated first-episode psychosis: an I123-IBZM SPECT study. Eur Neuropsychopharmacol 2011, 21:861-866.
20. Crawley J.C., Owens D.G., Crow T.J., Poulter M., Johnstone E.C., Smith T., et al. Dopamine D2 receptors in schizophrenia studied in vivo. Lancet 1986, 2:224-225. [Jul 26].
21. Dean B., Opeskin K., Pavey G., Hill C., Keks N. Changes in protein kinase C and adenylate cyclase in the temporal lobe from subjects with schizophrenia. J Neural Transm 1997, 104:1371-1381.
22. Dohlman H.G., Thorner J. RGS proteins and signaling by heterotrimeric G proteins. J Biol Chem 1997, 272:3871-3874.
23. Dong C., Wu G. G-protein-coupled receptor interaction with small GTPases. Methods Enzymol 2013, 522:97-108.
24. 11C]raclopride. Arch Gen Psychiatry 1990, 47:213-219.
25. Ferguson S.S., Downey W.E., Colapietro A.M., Barak L.S., Ménard L., Caron M.G. Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization. Science 1996, 271:363-366.
26. Fujita N., Nakahiro M., Fukuchi I., Saito K., Yoshida H. Effects of pertussis toxin on D2-dopamine receptor in rat striatum: evidence for coupling of Ni regulatory protein with D2-receptor. Brain Res 1985, 333:231-236.
27. George S.R., Watanabe M., Di Paolo T., Falardeau P., Labrie F., Seeman P. The functional state of the dopamine receptor in the anterior pituitary is in the high-affinity form. Endocrinology 1985, 117:690-697.
28. 11C]-(+)-PHNO PET study. Neuropsychopharmacology 2009, 34:1078-1086.
29. 3H]acetylcholine to muscarinic receptors. Regional distribution and modulation by guanine nucleotides. Mol Pharmacol 1985, 28:297-305.
30. Heald P.J. Analysis of radioactive phosphates in extracts of cerebral tissues. Biochem J 1956, 63:235-242.
31. Heald P.J. Guanosine di- and tri-phosphates in the phosphate metabolism of cerebral tissues promoted by electrical pulses. Biochem J 1957, 67:529-536.
32. Hillion J., Canals M., Torvinen M., Casado V., Scott R., Terasmaa A., et al. Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem 2002, 277:18091-18097.
33. Howes O.D., Kambeitz J., Kim E., Stahl D., Slifstein M., Abi-Dargham A., et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry 2012, 69(8):776-786.
34. Huganir R.L., Delcour A.H., Greengard P., Hess G.P. Phosphorylation of the nicotinic acetylcholine receptor regulates its rate of desensitization. Nature 1986, 321(6072):774-776.
35. Jensen J.B., Shimon H., Mørk A. Abnormal protein phosphorylation in post-mortem brain tissue from bipolar patients. J Neural Transm 2000, 107:501-509.
36. Johnson M.A., Lombroso P.J. A common STEP in the synaptic pathology of diverse neuropsychiatric disorders. Yale J Biol Med 2012, 85:481-490.
37. Kabbani N., Levenson R. Antipsychotic-induced alterations in D2 dopamine receptor interacting proteins within the cortex. Neuroreport 2006, 17:299-301.
38. Kabbani N., Negyessy L., Lin R., Goldman-Rakic P., Levenson R. Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor. J Neurosci 2002, 22:8476-8486.
39. 18F]fallypride positron emission tomography. Biol Psychiatry 2010, 68:634-641.
40. Kegeles L.S., Abi-Dargham A., Frankle W.G., Gil R., Cooper T.B., Slifstein M., et al. Increased synaptic dopamine function in associative regions of the striatum in schizophrenia. Arch Gen Psychiatry 2010, 67:231-239.
41. Kessler R.M., Woodward N.D., Riccardi P., Li R., Ansari M.S., Anderson S., et al. Dopamine D2 receptor levels in striatum, thalamus, substantia nigra, limbic regions, and cortex in schizophrenic subjects. Biol Psychiatry 2009, 65:1024-1031.
42. Kim K.M., Valenzano K.J., Robinson S.R., Yao W.D., Barak L.S., Caron M.G. Differential regulation of the dopamine D2 and D3 receptors by G protein-coupled receptor kinases and beta-arrestins. J Biol Chem 2001, 276:37409-37414.
43. King M.V., Seeman P., Marsden C.A., Fone K.C. Increased dopamine D2High receptors in rats reared in social isolation. Synapse 2009, 63:476-483.
44. 123I]-iodobenzamide SPECT study. Br J Psychiatry 1997, 171:574-577.
45. Ko F., Seeman P., Sun W.S., Kapur S. Dopamine D2 receptors internalize in their low-affinity state. Neuroreport 2002, 13:1017-1020.
46. Koh P.O., Undie A.S., Kabbani N., Levenson R., Goldman-Rakic P.S., Lidow M.S. Up-regulation of neuronal calcium sensor-1 (NCS-1) in the prefrontal cortex of schizophrenic and bipolar patients. Proc Natl Acad Sci U S A 2003, 100:313-317.
47. Krupnick J.G., Benovic J.L. The role of receptor kinases and arrestins in G protein-coupled receptor regulation. Annu Rev Pharmacol Toxicol 1998, 38:289-319.
48. Laruelle M. Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 2000, 20:423-451.
49. Laruelle M. The role of endogenous sensitization in the pathophysiology of schizophrenia: implications from recent brain imaging studies. Brain Res Brain Res Rev 2000, 31(2-3):371-384.
50. Laruelle M., Abi-Dargham A., Gil R., Kegeles L., Innis R. Increased dopamine transmission in schizophrenia: relationship to illness phases. Biol Psychiatry 1999, 46:56-72.
51. Lefkowitz R.J., Pitcher J., Krueger K., Daaka Y. Mechanisms of beta-adrenergic receptor desensitization and resensitization. Adv Pharmacol 1998, 42:416-420.
52. Lieberman J.A., Kane J.M., Alvir J. Provocative tests with psychostimulant drugs in schizophrenia. Psychopharmacology (Berl) 1987, 91:415-433.
53. Lin F.T., Krueger K.M., Kendall H.E., Daaka Y., Fredericks Z.L., Pitcher J.A., et al. Clathrin-mediated endocytosis of the beta-adrenergic receptor is regulated by phosphorylation/dephosphorylation of beta-arrestin1. J Biol Chem 1997, 272:31051-31057.
54. Lin R., Karpa K., Kabbani N., Goldman-Rakic P., Levenson R. Dopamine D2 and D3 receptors are linked to the actin cytoskeleton via interaction with filamin A. Proc Natl Acad Sci U S A 2001, 98:5258-5263.
55. Liu H., Heath S.C., Sobin C., Roos J.L., Galke B.L., Blundell M.L., et al. Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. Proc Natl Acad Sci U S A 2002, 99:3717-3722.
56. Marchese A., Chen C., Kim Y.M., Benovic J.L. The ins and outs of G protein-coupled receptor trafficking. Trends Biochem Sci 2003, 28(7):369-376.
57. 76Br-bromolisuride. Br J Psychiatry 1991, 158:346-350.
58. Martinot J.L., Paillère-Martinot M.L., Loc'h C., Lecrubier Y., Dao-Castellana M.H., Aubin F., et al. Central D2 receptors and negative symptoms of schizophrenia. Br J Psychiatry 1994, 164:27-34.
59. Mirnics K., Middleton F.A., Stanwood G.D., Lewis D.A., Levitt P. Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. Mol Psychiatry 2001, 6:293-301.
60. Namkung Y., Dipace C., Javitch J.A., Sibley D.R. G protein-coupled receptor kinase-mediated phosphorylation regulates post-endocytic trafficking of the D2 dopamine receptor. J Biol Chem 2009, 284(22):15038-15051.
61. Namkung Y., Dipace C., Urizar E., Javitch J.A., Sibley D.R. G protein-coupled receptor kinase-2 constitutively regulates D2 dopamine receptor expression and signaling independently of receptor phosphorylation. J Biol Chem 2009, 284(49):34103-34115.
62. 11C]N-methylspiperone. Psychiatry Res 1995, 61:67-83.
63. Okada F., Crow T.J., Roberts G.W. G-proteins (Gi, Go) in the basal ganglia of control and schizophrenic brain. J Neural Transm Gen Sect 1990, 79:227-234.
64. Okada F., Tokumitsu Y., Takahashi N., Crow T.J., Roberts G.W. Reduced concentrations of the alpha-subunit of GTP-binding protein Go in schizophrenic brain. J Neural Transm Gen Sect 1994, 95:95-104.
65. Perreault M.L., Hasbi A., Alijaniaram M., Fan T., Varghese G., Fletcher P.J., et al. The dopamine D1-D2 receptor heteromer localizes in dynorphin/enkephalin neurons: increased high affinity state following amphetamine and in schizophrenia. J Biol Chem 2010, 285:36625-36634.
66. Phan-Chan-Du A., Hemmerlin C., Krikorian D., Sakarellos-Daitsiotis M., Tsikaris V., Sakarellos C., et al. Solution conformation of the antibody-bound tyrosine phosphorylation site of the nicotinic acetylcholine receptor beta-subunit in its phosphorylated and nonphosphorylated states. Biochemistry 2003, 42(24):7371-7380.
67. 123I-IBZM single photon emission computerised tomography study. Br J Psychiatry 1994, 164:16-26.
68. Pippig S., Andexinger S., Lohse M.J. Sequestration and recycling of beta 2-adrenergic receptors permit receptor resensitization. Mol Pharmacol 1995, 47:666-676.
69. Revel F.G., Moreau J.L., Pouzet B., Mory R., Bradaia A., Buchy D., et al. A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight. Mol Psychiatry 2013, 18:543-556.
70. Rivero G., Gabilondo A.M., García-Sevilla J.A., Callado L.F., La Harpe R., Morentin B., et al. Brain RGS4 and RGS10 protein expression in schizophrenia and depression. Effect of drug treatment. Psychopharmacology (Berl) 2013, 226:177-188.
71. Rocheville M., Lange D.C., Kumar U., Patel S.C., Patel R.C., Patel Y.C. Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science 2000, 288:154-157.
72. 3H-(-)-N-n-propylnorapomorphine in mouse brain. Naunyn Schmiedebergs Arch Pharmacol 1989, 340:13-20.
73. Scarselli M., Novi F., Schallmach E., Lin R., Baragli A., Colzi A., et al. D2/D3 dopamine receptor heterodimers exhibit unique functional properties. J Biol Chem 2001, 276:30308-30314.
74. Seamans J.K., Lapish C.C., Durstewitz D. Comparing the prefrontal cortex of rats and primates: insights from electrophysiology. Neurotox Res 2008, 14(2-3):249-262.
75. Seeman P. Targeting the dopamine D2 receptor in schizophrenia. Expert Opin Ther Targets 2006, 10:515-531.
76. High receptors. Synapse 2007, 61:1013-1018.
77. Seeman P. Schizophrenia model of elevated D2High receptors: haloperidol reverses the amphetamine-induced elevation in dopamine D2High. Schizophr Res 2009, 109:191-192.
78. Seeman P. Dopamine D2High receptors measured ex vivo are elevated in amphetamine-sensitized animals. Synapse 2009, 63:186-192.
79. High receptors. CNS Neurosci Ther 2011, 17:118-132.
80. Seeman P. Dopamine agonist radioligand binds to both D2High and D2Low receptors, explaining why alterations in D2High are not detected in human brain scans. Synapse 2012, 66:88-93.
81. Seeman P., Chau-Wong M., Tedesco J., Wong K. Brain receptors for antipsychotic drugs and dopamine: direct binding assays. Proc Natl Acad Sci U S A 1975, 72:4376-4380.
82. Seeman P., Lee T., Chau-Wong M., Wong K. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 1976, 261:717-719.
83. Seeman P., Bzowej N.H., Guan H.C., Bergeron C., Reynolds G.P., Bird E.D., et al. Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer's, Parkinson's, and Huntington's diseases. Neuropsychopharmacology 1987, 1:5-15.
84. Seeman P., Niznik H.B., Guan H.C., Booth G., Ulpian C. Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain. Proc Natl Acad Sci U S A 1989, 86:10156-10160.
85. Seeman P., Weinshenker D., Quirion R., Srivastava L.K., Bhardwaj S.K., Grandy D.K., et al. Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis. Proc Natl Acad Sci U S A 2005, 102:3513-3518.
86. Seeman P., Schwarz J., Chen J.F., Szechtman H., Perreault M., McKnight G.S., et al. Psychosis pathways converge via D2high dopamine receptors. Synapse 2006, 60:319-346.
87. Senogles S.E., Spiegel A.M., Padrell E., Iyengar R., Caron M.G. Specificity of receptor-G protein interactions. Discrimination of Gi subtypes by the D2 dopamine receptor in a reconstituted system. J Biol Chem 1990, 265:4507-4514.
88. Silvestri S., Seeman M.V., Negrete J.C., Houle S., Shammi C.M., Remington G.J., et al. Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study. Psychopharmacology (Berl) 2000, 152:174-180.
89. Smith F.D., Oxford G.S., Milgram S.L. Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein. J Biol Chem 1999, 274:19894-19900.
90. Sromek A.W., Neumeyer J.L., Yu-Gui S., Zhang T., Seeman P., George S.R., et al. Development of high affinity, highly selective agonist ligands for positron emission tomography imaging of the dopamine D2 receptor. 243rd Am. Chem. Soc. National Meeting, San Diego, CA March 28, 2012 paper # 382 2012.
91. Stefanis N.C., Dragovic M., Power B.D., Jablensky A., Castle D., Morgan V.A. Age at initiation of cannabis use predicts age at onset of psychosis: the 7- to 8-year trend. Schizophr Bull 2013, 39(2):251-254.
92. Talvik M., Nordström A.L., Okubo Y., Olsson H., Borg J., Halldin C., et al. Dopamine D2 receptor binding in drug-naïve patients with schizophrenia examined with raclopride-C11 and positron emission tomography. Psychiatry Res 2006, 148:165-173.
93. Thibault D., Albert P.R., Pineyro G., Trudeau L.É. Neurotensin triggers dopamine D2 receptor desensitization through a protein kinase C and beta-arrestin1-dependent mechanism. J Biol Chem 2011, 286(11):9174-9184.
94. Thompson J.L., Urban N., Slifstein M., Xu X., Kegeles L.S., Girgis R.R., et al. Striatal dopamine release in schizophrenia comorbid with substance dependence. Mol Psychiatry 2012, 10.1038/mp.2012.109.
95. Van Rossum J.M. The significance of dopamine-receptor blockade for the action of neuroleptic drugs. Neuro-Psycho-Pharmacology, Proceedings of the Fifth International Congress of the Collegium Internationale Neuro-Psycho-pharmacologicum, Washington, March, 1966 1967, 321-329. Excerpta Medica Foundation, Amsterdam. H. Brill, J.O. Cole, P. Deniker, H. Hippius, P.B. Bradley (Eds.).
96. Wang M., Pei L., Fletcher P.J., Kapur S., Seeman P., Liu F. Schizophrenia, amphetamine-induced sensitized state and acute amphetamine exposure all show a common alteration: increased dopamine D2 receptor dimerization. Mol Brain 2010, 3:25-34.
97. Wiesner A., Fuhrer C. Regulation of nicotinic acetylcholine receptors by tyrosine kinases in the peripheral and central nervous system: same players, different roles. Cell Mol Life Sci 2006, 63(23):2818-2828.
98. Wolinsky T.D., Swanson C.J., Smith K.E., Zhong H., Borowsky B., Seeman P., et al. The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia. Genes Brain Behav 2007, 6:628-639.
99. Wong D.F., Wagner H.N., Tune L.E., Dannals R.F., Pearlson G.D., Links J.M., et al. Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 1986, 234:1558-1563.
100. Wreggett K.A., Seeman P. Agonist high- and low-affinity states of the D2-dopamine receptor in calf brain. Partial conversion by guanine nucleotide. Mol Pharmacol 1984, 25:10-17.
101. Wu Y., Buranda T., Simons P.C., Lopez G.P., McIntire W.E., Garrison J.C., et al. Rapid-mix flow cytometry measurements of subsecond regulation of G protein-coupled receptor ternary complex dynamics by guanine nucleotides. Anal Biochem 2007, 371:10-20.
102. Xiao M.F., Xu J.C., Tereshchenko Y., Novak D., Schachner M., Kleene R. Neural cell adhesion molecule modulates dopaminergic signaling and behavior by regulating dopamine D2 receptor internalization. J Neurosci 2009, 29:14752-14763.
103. Yang Y.K., Yu L., Yeh T.L., Chiu N.T., Chen P.S., Lee I.H. Associated alterations of striatal dopamine D2/D3 receptor and transporter binding in drug-naive patients with schizophrenia: a dual-isotope SPECT study. Am J Psychiatry 2004, 161:1496-1498.
104. Yger M., Girault J.A. DARPP-32, jack of all trades. . . Master of which?. Front Behav Neurosci 2011, 5:56.
105. Zahniser N.R., Molinoff P.B. Effect of guanine nucleotides on striatal dopamine receptors. Nature 1978, 275:453-455.
106. Zawarynski P., Tallerico T., Seeman P., Lee S.P., O'Dowd B.F., George S.R. Dopamine D2 receptor dimers in human and rat brain. FEBS Lett 1998, 441:383-386.
107. Zhao P., Cladman W., Van Tol H.H.M., Chidiac P. Fine-tuning of GPCR signals by intracellular G protein modulators. Prog Mol Biol Transl Sci 2013, 115:421-453.