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Current perspectives on the selective regulation of dopamine D2 and D3 receptors

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Abstract

Among the characterized dopamine receptor subtypes, D2 receptor (D2R) and D3 receptor (D3R) are the main targets of neuroleptics that are currently in use. In particular, D3R is closely related to the etiology of schizophrenia and drug addiction. The spatial expression patterns of D2R and D3R are distinct in certain areas of the brain. D2R are heavily expressed in the regions responsible for motor functions, whereas D3R are more selectively expressed in the limbic regions, which are associated with cognitive and emotional functions. Therefore, disturbances in the motor and endocrine functions, which are the most serious problems caused by the current neuroleptics, are likely to result from the non-selective blockade of D2R. Selective regulation of D3R is needed to separate the desired therapeutic activities from unwanted side effects that result from promiscuous blockade of other receptors. D2R and D3R possess high sequence homology and employ similar signaling pathways, and it is difficult to selectively regulate them. In this review, we discuss the signaling mechanisms, intracellular trafficking, and desensitization properties of D2R and D3R. In addition, the proteins interacting with D2R or D3R are discussed in relation to their roles in the regulation of receptor functions, followed by the current status of the development of selective D3R ligands.

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References

  • Accili, D., Fishburn, C. S., Drago, J., Steiner, H., Lachowicz, J. E., Park, B. H., Gauda, E. B., Lee, E. J., Cool, M. H., Sibley, D. R., Gerfen, C. R., Westphal, H., and Fuchs, S., A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice., Proc. Natl. Acad. Sci. U.S.A., 93, 1945–1949 (1996).

    Article  CAS  PubMed  Google Scholar 

  • Anderson, D. W., Neavin, T., Smith, J. A., and Schneider, J. S., Neuroprotective effects of pramipexole in young and aged MPTP-treated mice. Brain Res., 905, 44–53 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Baik, J. H., Picetti, R., Saiardi, A., Thiriet, G., Dierich, A., Depaulis, A., Le Meur, M., and Borrelli, E., Parkinsonianlike locomotor impairment in mice lacking dopamine D2 receptors. Nature, 377, 424–428 (1995).

    Article  CAS  PubMed  Google Scholar 

  • Barak, L. S., Menard, L., Ferguson, S. S., Colapietro, A. M., and Caron, M. G., The conserved seven-transmembrane sequence NP(X)2,3Y of the G-protein-coupled receptor superfamily regulates multiple properties of the beta 2-adrenergic receptor. Biochemistry, 34, 15407–15414 (1995).

    Article  CAS  PubMed  Google Scholar 

  • Bartlett, S. E., Enquist, J., Hopf, F. W., Lee, J. H., Gladher, F., Kharazia, V., Waldhoer, M., Mailliard, W. S., Armstrong, R., Bonci, A., and Whistler, J. L., Dopamine responsiveness is regulated by targeted sorting of D2 receptors. Proc. Natl. Acad. Sci. U.S.A., 102, 11521–11526 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Basile, M., Lin, R., Kabbani, N., Karpa, K., Kilimann, M., Simpson, I., and Kester, M., Paralemmin interacts with D3 dopamine receptors: implications for membrane localization and cAMP signaling. Arch. Biochem. Biophys., 446, 60–68 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Beaulieu, J. M., Sotnikova, T. D., Yao, W. D., Kockeritz, L., Woodgett, J. R., Gainetdinov, R. R., and Caron, M. G., Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Proc. Natl. Acad. Sci. U.S.A., 101, 5099–5104 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Beaulieu, J. M., Sotnikova, T. D., Marion, S., Lefkowitz, R. J., Gainetdinov, R. R., and Caron, M. G., An Akt/betaarrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell, 122, 261–273 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Beaulieu, J. M., Marion, S., Rodriguiz, R. M., Medvedev, I. O., Sotnikova, T. D., Ghisi, V., Wetsel, W. C., Lefkowitz, R. J., Gainetdinov, R. R., and Caron, M. G., A beta-arrestin 2 signaling complex mediates lithium action on behavior. Cell, 132, 125–136 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Benovic, J. L., Kuhn, H., Weyand, I., Codina, J., Caron, M. G., and Lefkowitz, R. J., Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein). Proc. Natl. Acad. Sci. U.S.A., 84, 8879–8882 (1987).

    Article  CAS  PubMed  Google Scholar 

  • Benovic, J. L., DeBlasi, A., Stone, W. C., Caron, M. G., and Lefkowitz, R. J., Beta-adrenergic receptor kinase: primary structure delineates a multigene family. Science, 246, 235–240 (1989).

    Article  CAS  PubMed  Google Scholar 

  • Beom, S., Cheong, D., Torres, G., Caron, M. G., and Kim, K. M., Comparative studies of molecular mechanisms of dopamine D2 and D3 receptors for the activation of extracellular signal-regulated kinase. J. Biol. Chem., 279, 28304–28314 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Binda, A. V., Kabbani, N., Lin, R., and Levenson, R., D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1N. Mol. Pharmacol., 62, 507–513 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Binda, A. V., Kabbani, N., and 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., 69, 1451–1461 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Boeckler, F., Leng, A., Mura, A., Bettinetti, L., Feldon, J., Gmeiner, P., and Ferger, B., Attenuation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity by the novel selective dopamine D3-receptor partial agonist FAUC 329 predominantly in the nucleus accumbens of mice. Biochem. Pharmacol., 66, 1025–1032 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Boeckler, F. and Gmeiner, P., The structural evolution of dopamine D3 receptor ligands: structure-activity relationships and selected neuropharmacological aspects. Pharmacol. Ther., 112, 281–333 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Boeckler, F. and Gmeiner, P., Dopamine D3 receptor ligands: recent advances in the control of subtype selectivity and intrinsic activity. Biochim. Biophys. Acta, 1768, 871–887 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Bofill-Cardona, E., Kudlacek, O., Yang, Q., Ahorn, H., Freissmuth, M., and Nanoff, C., Binding of calmodulin to the D2-dopamine receptor reduces receptor signaling by arresting the G protein activation switch. J. Biol. Chem., 275, 32672–32680 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Brown, J. H. and Makman, M. H., Stimulation by dopamine of adenylate cyclase in retinal homogenates and of adenosine-3′:5′-cyclic monophosphate formation in intact retina. Proc. Natl. Acad. Sci. U.S.A., 69, 539–543 (1972).

    Article  CAS  PubMed  Google Scholar 

  • Bunzow, J. R., Van Tol, H. H., Grandy, D. K., Albert, P., Salon, J., Christie, M., Machida, C. A., Neve, K. A., and Civelli, O., Cloning and expression of a rat D2 dopamine receptor cDNA. Nature, 336, 783–787 (1988).

    Article  CAS  PubMed  Google Scholar 

  • Caine, S. B. and Koob, G. F., Modulation of cocaine self-administration in the rat through D-3 dopamine receptors. Science, 260, 1814–1816 (1993).

    Article  CAS  PubMed  Google Scholar 

  • Carlsson, A., Lindqvist, M., and Magnusson, T., 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature, 180, 1200 (1957).

    Article  CAS  PubMed  Google Scholar 

  • Chen, C. H., Liu, M. Y., Wei, F. C., Koong, F. J., Hwu, H. G., and Hsiao, K. J., Further evidence of no association between Ser9Gly polymorphism of dopamine D3 receptor gene and schizophrenia. Am. J. Med. Genet., 74, 40–43 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Chio, C. L., Lajiness, M. E., and Huff, R. M., Activation of heterologously expressed D3 dopamine receptors: comparison with D2 dopamine receptors. Mol. Pharmacol., 45, 51–60 (1994).

    CAS  PubMed  Google Scholar 

  • Cho, D. I., Oak, M. H., Yang, H. J., Choi, H. K., Janssen, G. M., and Kim, K. M., Direct and biochemical interaction between dopamine D3 receptor and elongation factor-1Bbetagamma. Life Sci., 73, 2991–3004 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Cho, D. I., Beom, S., Van Tol, H. H., Caron, M. G., and Kim, K. M., Characterization of the desensitization properties of five dopamine receptor subtypes and alternatively spliced variants of dopamine D2 and D4 receptors. Biochem. Biophys. Res. Commun., 350, 634–640 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Cho, D. I., Zheng, M., Min, C. H., Ma, L., Kurose, H., Park, J. H., and Kim, K. M., Agonist-induced endocytosis and receptor phosphorylation mediate resensitization of dopamine D(2) receptors. Mol. Endocrinol., 24, 574–586 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Cho, E. Y., Cho, D. I., Park, J. H., Kurose, H., Caron, M. G., and Kim, K. M., Roles of protein kinase C and actin-binding protein 280 in the regulation of intracellular trafficking of dopamine D3 receptor. Mol. Endocrinol., 21, 2242–2254 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Cho, E. Y., Park, J. H., and Kim, K. M., Roles of conserved intracellular sequences regions for the proper expression of dopamine D(2) and D(3) receptors. Arch. Pharm. Res., 31, 634–639 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Cunnah, D. and Besser, M., Management of prolactinomas. Clin. Endocrinol. (Oxf.), 34, 231–235 (1991).

    Article  CAS  Google Scholar 

  • Cussac, D., Newman-Tancredi, A., Pasteau, V., and Millan, M. J., Human dopamine D(3) receptors mediate mitogenactivated protein kinase activation via a phosphatidylinositol 3-kinase and an atypical protein kinase Cdependent mechanism. Mol. Pharmacol., 56, 1025–1030 (1999).

    CAS  PubMed  Google Scholar 

  • Dal Toso, R., Sommer, B., Ewert, M., Herb, A., Pritchett, D. B., Bach, A., Shivers, B. D., and Seeburg, P. H., The dopamine D2 receptor: two molecular forms generated by alternative splicing. EMBO J., 8, 4025–4034 (1989).

    Google Scholar 

  • Daly, S. A. and Waddington, J. L., Behavioural effects of the putative D-3 dopamine receptor agonist 7-OH-DPAT in relation to other “D-2-like” agonists. Neuropharmacology, 32, 509–510 (1993).

    Article  CAS  PubMed  Google Scholar 

  • Damsma, G., Bottema, T., Westerink, B. H., Tepper, P. G., Dijkstra, D., Pugsley, T. A., MacKenzie, R. G., Heffner, T. G., and Wikstrom, H., Pharmacological aspects of R-(+)-7-OH-DPAT, a putative dopamine D3 receptor ligand. Eur. J. Pharmacol., 249, R9–10 (1993).

    Article  CAS  PubMed  Google Scholar 

  • De Camilli, P., Macconi, D., and Spada, A., Dopamine inhibits adenylate cyclase in human prolactin-secreting pituitary adenomas. Nature, 278, 252–254 (1979).

    Article  PubMed  Google Scholar 

  • Dearry, A., Gingrich, J. A., Falardeau, P., Fremeau, R. T., Jr., Bates, M. D., and Caron, M. G., Molecular cloning and expression of the gene for a human D1 dopamine receptor. Nature, 347, 72–76 (1990).

    Article  CAS  PubMed  Google Scholar 

  • DeWire, S. M., Ahn, S., Lefkowitz, R. J., and Shenoy, S. K., Beta-arrestins and cell signaling. Annu. Rev. Physiol., 69, 483–510 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Diaz, J., Pilon, C., Le Foll, B., Gros, C., Triller, A., Schwartz, J. C., and Sokoloff, P., Dopamine D3 receptors expressed by all mesencephalic dopamine neurons. J. Neurosci., 20, 8677–8684 (2000).

    CAS  PubMed  Google Scholar 

  • Everett, P. B. and Senogles, S. E., D3 dopamine receptor activates phospholipase D through a pertussis toxin-insensitive pathway. Neurosci. Lett., 371, 34–39 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Everett, P. B. and Senogles, S. E., D3 dopamine receptor signals to activation of phospholipase D through a complex with Rho. J. Neurochem., 112, 963–971 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Ferguson, S. S., Downey, W. E., Colapietro, A. M., Barak, L. S., Menard, L., and Caron, M. G., Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization. Science, 271, 363–366 (1996).

    Article  CAS  PubMed  Google Scholar 

  • Ferguson, S. S. and Caron, M. G., G protein-coupled receptor adaptation mechanisms. Semin. Cell Dev. Biol., 9, 119–127 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Fishburn, C. S., Belleli, D., David, C., Carmon, S., and Fuchs, S., A novel short isoform of the D3 dopamine receptor generated by alternative splicing in the third cytoplasmic loop. J. Biol. Chem., 268, 5872–5878 (1993).

    CAS  PubMed  Google Scholar 

  • Freedman, S. B., Patel, S., Marwood, R., Emms, F., Seabrook, G. R., Knowles, M. R., and McAllister, G., Expression and pharmacological characterization of the human D3 dopamine receptor. J. Pharmacol. Exp. Ther., 268, 417–426 (1994).

    CAS  PubMed  Google Scholar 

  • Ganz, M. B., Pachter, J. A., and Barber, D. L., Multiple receptors coupled to adenylate cyclase regulate Na-H exchange independent of cAMP. J. Biol. Chem., 265, 8989–8992 (1990).

    CAS  PubMed  Google Scholar 

  • Giros, B., Sokoloff, P., Martres, M. P., Riou, J. F., Emorine, L. J., and Schwartz, J. C., Alternative splicing directs the expression of two D2 dopamine receptor isoforms. Nature, 342, 923–926 (1989).

    Article  CAS  PubMed  Google Scholar 

  • Giros, B., Martres, M. P., Sokoloff, P., and Schwartz, J. C., Gene cloning of human dopaminergic D3 receptor and identification of its chromosome. C. R. Acad. Sci. III, 311, 501–508 (1990).

    CAS  PubMed  Google Scholar 

  • Giros, B., Martres, M. P., Pilon, C., Sokoloff, P., and Schwartz, J. C., Shorter variants of the D3 dopamine receptor produced through various patterns of alternative splicing. Biochem. Biophys. Res. Commun., 176, 1584–1592 (1991).

    Article  CAS  PubMed  Google Scholar 

  • Goldman, D., Urbanek, M., Guenther, D., Robin, R., and Long, J. C., A functionally deficient DRD2 variant [Ser311Cys] is not linked to alcoholism and substance abuse. Alcohol, 16, 47–52 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Guo, W., Shi, L., and Javitch, J. A., The fourth transmembrane segment forms the interface of the dopamine D2 receptor homodimer. J. Biol. Chem., 278, 4385–4388 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Gupta, S. K. and Mishra, R. K., The effect of dopamine D1 and D2 receptor agonists on inositol phosphate turnover in rat striatal slices. Biochem. Int., 22, 887–894 (1990).

    CAS  PubMed  Google Scholar 

  • Gurevich, E. V. and Joyce, J. N., Distribution of dopamine D3 receptor expressing neurons in the human forebrain: comparison with D2 receptor expressing neurons. Neuropsychopharmacology, 20, 60–80 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Gyertyan, I., Kiss, B., Gal, K., Laszlovszky, I., Horvath, A., Gemesi, L. I., Saghy, K., Pasztor, G., Zajer, M., Kapas, M., Csongor, E. A., Domany, G., Tihanyi, K., and Szombathelyi, Z., Effects of RGH-237 [N-{4-[4-(3-aminocarbonyl-phenyl)-piperazin-1-yl]-butyl}-4-bromo-benzamide], an orally active, selective dopamine D(3) receptor partial agonist in animal models of cocaine abuse. J. Pharmacol. Exp. Ther., 320, 1268–1278 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Haadsma-Svensson, S. R., Cleek, K. A., Dinh, D. M., Duncan, J. N., Haber, C. L., Huff, R. M., Lajiness, M. E., Nichols, N. F., Smith, M. W., Svensson, K. A., Zaya, M. J., Carlsson, A., and Lin, C. H., Dopamine D(3) receptor antagonists. 1. Synthesis and structure-activity relationships of 5,6-dimethoxy-N-alkyl- and N-alkylaryl-substituted 2-aminoindans. J. Med. Chem., 44, 4716–4732 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Hackling, A. E. and Stark, H., Dopamine D3 receptor ligands with antagonist properties. Chembiochem, 3, 946–961 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Hammond, S. M., Altshuller, Y. M., Sung, T. C., Rudge, S. A., Rose, K., Engebrecht, J., Morris, A. J., and Frohman, M. A., Human ADP-ribosylation factor-activated phosphatidylcholine-specific phospholipase D defines a new and highly conserved gene family. J. Biol. Chem., 270, 29640–29643 (1995).

    Article  CAS  PubMed  Google Scholar 

  • Hammond, S. M., Jenco, J. M., Nakashima, S., Cadwallader, K., Gu, Q., Cook, S., Nozawa, Y., Prestwich, G. D., Frohman, M. A., and Morris, A. J., Characterization of two alternately spliced forms of phospholipase D1. Activation of the purified enzymes by phosphatidylinositol 4,5-bisphosphate, ADP-ribosylation factor, and Rho family monomeric GTPbinding proteins and protein kinase C-alpha. J. Biol. Chem., 272, 3860–3868 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Hannan, M. A., Kabbani, N., Paspalas, C. D., and Levenson, R., Interaction with dopamine D2 receptor enhances expression of transient receptor potential channel 1 at the cell surface. Biochim. Biophys. Acta, 1778, 974–982 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Hasbi, A., O’Dowd, B. F., and George, S. R., Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms. Curr. Opin. Pharmacol., 10, 93–99 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Heidbreder, C. A. and Newman, A. H., Current perspectives on selective dopamine D(3) receptor antagonists as pharmacotherapeutics for addictions and related disorders. Ann. N. Y. Acad. Sci., 1187, 4–34 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Hinshaw, J. E. and Schmid, S. L., Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding. Nature, 374, 190–192 (1995).

    Article  CAS  PubMed  Google Scholar 

  • Holmes, A., Lachowicz, J. E., and Sibley, D. R., Phenotypic analysis of dopamine receptor knockout mice; recent insights into the functional specificity of dopamine receptor subtypes. Neuropharmacology, 47, 1117–1134 (2004).

    CAS  PubMed  Google Scholar 

  • Itokawa, M., Arinami, T., Futamura, N., Hamaguchi, H., and Toru, M., A structural polymorphism of human dopamine D2 receptor, D2(Ser311—>Cys). Biochem. Biophys. Res. Commun., 196, 1369–1375 (1993).

    Article  CAS  PubMed  Google Scholar 

  • Ivins, K. J., Luedtke, R. R., Artymyshyn, R. P., and Molinoff, P. B., Regulation of dopamine D2 receptors in a novel cell line (SUP1). Mol. Pharmacol., 39, 531–539 (1991).

    CAS  PubMed  Google Scholar 

  • Jeanneteau, F., Diaz, J., Sokoloff, P., and Griffon, N., Interactions of GIPC with dopamine D2, D3 but not D4 receptors define a novel mode of regulation of G protein-coupled receptors. Mol. Biol. Cell, 15, 696–705 (2004a).

    Article  CAS  PubMed  Google Scholar 

  • Jeanneteau, F., Guillin, O., Diaz, J., Griffon, N., and Sokoloff, P., GIPC recruits GAIP (RGS19) to attenuate dopamine D2 receptor signaling. Mol. Biol. Cell, 15, 4926–4937 (2004b).

    Article  CAS  PubMed  Google Scholar 

  • Jeanneteau, F., Funalot, B., Jankovic, J., Deng, H., Lagarde, J. P., Lucotte, G., and Sokoloff, P., A functional variant of the dopamine D3 receptor is associated with risk and ageat-onset of essential tremor. Proc. Natl. Acad. Sci. U.S.A., 103, 10753–10758 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Joseph, J. D., Wang, Y. M., Miles, P. R., Budygin, E. A., Picetti, R., Gainetdinov, R. R., Caron, M. G., and Wightman, R. M., Dopamine autoreceptor regulation of release and uptake in mouse brain slices in the absence of D(3) receptors. Neuroscience, 112, 39–49 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Joyce, J. N., Dopamine D3 receptor as a therapeutic target for antipsychotic and antiparkinsonian drugs. Pharmacol. Ther., 90, 231–259 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Joyce, J. N. and Millan, M. J., Dopamine D3 receptor antagonists as therapeutic agents. Drug Discov. Today, 10, 917–925 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Jung, M. Y., Skryabin, B. V., Arai, M., Abbondanzo, S., Fu, D., Brosius, J., Robakis, N. K., Polites, H. G., Pintar, J. E., and Schmauss, C., Potentiation of the D2 mutant motor phenotype in mice lacking dopamine D2 and D3 receptors. Neuroscience, 91, 911–924 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Kabbani, N. and Levenson, R., Antipsychotic-induced alterations in D2 dopamine receptor interacting proteins within the cortex. Neuroreport., 17, 299–301 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Kebabian, J. W. and Calne, D. B., Multiple receptors for dopamine. Nature, 277, 93–96 (1979).

    Article  CAS  PubMed  Google Scholar 

  • Kelly, M. A., Rubinstein, M., Asa, S. L., Zhang, G., Saez, C., Bunzow, J. R., Allen, R. G., Hnasko, R., Ben-Jonathan, N., Grandy, D. K., and Low, M. J., Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice. Neuron, 19, 103–113 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Kim, K. M., Valenzano, K. J., Robinson, S. R., Yao, W. D., Barak, L. S., and Caron, M. G., Differential regulation of the dopamine D2 and D3 receptors by G protein-coupled receptor kinases and beta-arrestins. J. Biol. Chem., 276, 37409–37414 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Kim, K. M., Gainetdinov, R. R., Laporte, S. A., Caron, M. G., and Barak, L. S., G protein-coupled receptor kinase regulates dopamine D3 receptor signaling by modulating the stability of a receptor-filamin-beta-arrestin complex. A case of autoreceptor regulation. 280, 12780 (2005).

    Google Scholar 

  • Kim, K. M. and Caron, M. G., Complementary roles of the DRY motif and C-terminus tail of GPCRS for G protein coupling and beta-arrestin interaction. Biochem. Biophys. Res. Commun., 366, 42–47 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Kim, O. J., Ariano, M. A., Namkung, Y., Marinec, P., Kim, E., Han, J., and Sibley, D. R., D2 dopamine receptor expression and trafficking is regulated through direct interactions with ZIP. J. Neurochem., 106, 83–95 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Kim, S. J., Kim, M. Y., Lee, E. J., Ahn, Y. S., and Baik, J. H., Distinct regulation of internalization and mitogen-activated protein kinase activation by two isoforms of the dopamine D2 receptor. Mol. Endocrinol., 18, 640–652 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Kodaki, T. and Yamashita, S., Cloning, expression, and characterization of a novel phospholipase D complementary DNA from rat brain. J. Biol. Chem., 272, 11408–11413 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Koeltzow, T. E., Xu, M., Cooper, D. C., Hu, X. T., Tonegawa, S., Wolf, M. E., and White, F. J., Alterations in dopamine release but not dopamine autoreceptor function in dopamine D3 receptor mutant mice. J. Neurosci., 18, 2231–2238 (1998).

    CAS  PubMed  Google Scholar 

  • Kovacs, J. J., Hara, M. R., Davenport, C. L., Kim, J., and Lefkowitz, R. J., Arrestin development: emerging roles for beta-arrestins in developmental signaling pathways. Dev. Cell, 17, 443–458 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Krueger, K. M., Daaka, Y., Pitcher, J. A., and Lefkowitz, R. J., The role of sequestration in G protein-coupled receptor resensitization. Regulation of beta2-adrenergic receptor dephosphorylation by vesicular acidification. J. Biol. Chem., 272, 5–8 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Kuzhikandathil, E. V. and Oxford, G. S., Activation of human D3 dopamine receptor inhibits P/Q-type calcium channels and secretory activity in AtT-20 cells. J. Neurosci., 19, 1698–1707 (1999).

    CAS  PubMed  Google Scholar 

  • Lan, H., Liu, Y., Bell, M. I., Gurevich, V. V., and Neve, K. A., A dopamine D2 receptor mutant capable of G proteinmediated signaling but deficient in arrestin binding. Mol. Pharmacol., 75, 113–123 (2009a).

    Article  CAS  PubMed  Google Scholar 

  • Lan, H., Teeter, M. M., Gurevich, V. V., and Neve, K. A., An intracellular loop 2 amino acid residue determines differential binding of arrestin to the dopamine D2 and D3 receptors. Mol. Pharmacol., 75, 19–26 (2009b).

    Article  CAS  PubMed  Google Scholar 

  • Lannfelt, L., Sokoloff, P., Martres, M. P., Pilon, C., Giros, B., Jonsson, E., Sedvall, G., and Schwartz, J. C., Amino acid substitution in the dopamine D3 receptor as a useful polymorphism for investigating psychiatric disorders. Psychiatr. Genet., 2, 249–256 (1992).

    Article  Google Scholar 

  • Laporte, S. A., Oakley, R. H., Zhang, J., Holt, J. A., Ferguson, S. S., Caron, M. G., and Barak, L. S., The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis. Proc. Natl. Acad. Sci. U.S.A., 96, 3712–3717 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Lee, S. P., So, C. H., Rashid, A. J., Varghese, G., Cheng, R., Lanca, A. J., O’Dowd, B. F., and George, S. R., Dopamine D1 and D2 receptor Co-activation generates a novel phospholipase C-mediated calcium signal. J. Biol. Chem., 279, 35671–35678 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Lee, T., Seeman, P., Rajput, A., Farley, I. J., and Hornykiewicz, O., Receptor basis for dopaminergic supersensitivity in Parkinson’s disease. Nature, 273, 59–61 (1978).

    Article  CAS  PubMed  Google Scholar 

  • Lenz, C., Boeckler, F., Hubner, H., and Gmeiner, P., Analogues of FAUC 73 revealing new insights into the structural requirements of nonaromatic dopamine D3 receptor agonists. Bioorg. Med. Chem., 12, 113–117 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Levesque, D., Diaz, J., Pilon, C., Martres, M. P., Giros, B., Souil, E., Schott, D., Morgat, J. L., Schwartz, J. C., and Sokoloff, P., Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin. Proc. Natl. Acad. Sci. U.S.A., 89, 8155–8159 (1992).

    Article  CAS  PubMed  Google Scholar 

  • Li, M., Bermak, J. C., Wang, Z. W., and Zhou, Q. Y., Modulation of dopamine D(2) receptor signaling by actin-binding protein (ABP-280). Mol. Pharmacol., 57, 446–452 (2000).

    CAS  PubMed  Google Scholar 

  • Li, M., Li, C., Weingarten, P., Bunzow, J. R., Grandy, D. K., and Zhou, Q. Y., Association of dopamine D(3) receptors with actin-binding protein 280 (ABP-280). Biochem. Pharmacol., 63, 859–863 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Lin, R., Karpa, K., Kabbani, N., Goldman-Rakic, P., and 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., 98, 5258–5263 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Liu, X. Y., Chu, X. P., Mao, L. M., Wang, M., Lan, H. X., Li, M. H., Zhang, G. C., Parelkar, N. K., Fibuch, E. E., Haines, M., Neve, K. A., Liu, F., Xiong, Z. G., and Wang, J. Q., Modulation of D2R-NR2B interactions in response to cocaine. Neuron, 52, 897–909 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Liu, X. Y., Mao, L. M., Zhang, G. C., Papasian, C. J., Fibuch, E. E., Lan, H. X., Zhou, H. F., Xu, M., and Wang, J. Q., Activity-dependent modulation of limbic dopamine D3 receptors by CaMKII. Neuron, 61, 425–438 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Liu, Y., Buck, D. C., Macey, T. A., Lan, H., and Neve, K. A., Evidence that calmodulin binding to the dopamine D2 receptor enhances receptor signaling. J. Recept. Signal Transduct. Res., 27, 47–65 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Liu, Y., Buck, D. C., and Neve, K. A., Novel interaction of the dopamine D2 receptor and the Ca2+ binding protein S100B: role in D2 receptor function. Mol. Pharmacol., 74, 371–378 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Lohse, M. J., Benovic, J. L., Codina, J., Caron, M. G., and Lefkowitz, R. J., beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science, 248, 1547–1550 (1990).

    Article  CAS  PubMed  Google Scholar 

  • Lucotte, G., Lagarde, J. P., Funalot, B., and Sokoloff, P., Linkage with the Ser9Gly DRD3 polymorphism in essential tremor families. Clin. Genet., 69, 437–440 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Lundstrom, K. and Turpin, M. P., Proposed schizophreniarelated gene polymorphism: expression of the Ser9Gly mutant human dopamine D3 receptor with the Semliki Forest virus system. Biochem. Biophys. Res. Commun., 225, 1068–1072 (1996).

    Article  CAS  PubMed  Google Scholar 

  • Millan, M. J., Audinot, V., Rivet, J. M., Gobert, A., Vian, J., Prost, J. F., Spedding, M., and Peglion, J. L., S 14297, a novel selective ligand at cloned human dopamine D3 receptors, blocks 7-OH-DPAT-induced hypothermia in rats. Eur. J. Pharmacol., 260, R3–5 (1994).

    Article  CAS  PubMed  Google Scholar 

  • Millan, M. J., Di Cara, B., Dekeyne, A., Panayi, F., De Groote, L., Sicard, D., Cistarelli, L., Billiras, R., and Gobert, A., Selective blockade of dopamine D(3) versus D(2) receptors enhances frontocortical cholinergic transmission and social memory in rats: a parallel neurochemical and behavioural analysis. J. Neurochem., 100, 1047–1061 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Monsma, F. J., Jr., McVittie, L. D., Gerfen, C. R., Mahan, L. C., and Sibley, D. R., Multiple D2 dopamine receptors produced by alternative RNA splicing. Nature, 342, 926–929 (1989).

    Article  CAS  PubMed  Google Scholar 

  • Namkung, Y. and Sibley, D. R., Protein kinase C mediates phosphorylation, desensitization, and trafficking of the D2 dopamine receptor. J. Biol. Chem., 279, 49533–49541 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Neve, K. A., Kozlowski, M. R., and Rosser, M. P., Dopamine D2 receptor stimulation of Na+/H+ exchange assessed by quantification of extracellular acidification. J. Biol. Chem., 267, 25748–25753 (1992).

    CAS  PubMed  Google Scholar 

  • Newman, A. H., Grundt, P., and Nader, M. A., Dopamine D3 receptor partial agonists and antagonists as potential drug abuse therapeutic agents. J. Med. Chem., 48, 3663–3679 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Olson, J. K. and Grose, C., Endocytosis and recycling of varicella-zoster virus Fc receptor glycoprotein gE: internalization mediated by a YXXL motif in the cytoplasmic tail. J. Virol., 71, 4042–4054 (1997).

    CAS  PubMed  Google Scholar 

  • Pilon, C., Levesque, D., Dimitriadou, V., Griffon, N., Martres, M. P., Schwartz, J. C., and Sokoloff, P., Functional coupling of the human dopamine D3 receptor in a transfected NG 108-15 neuroblastoma-glioma hybrid cell line. Eur. J. Pharmacol., 268, 129–139 (1994).

    Article  CAS  PubMed  Google Scholar 

  • Pizzi, M., D’Agostini, F., Da Prada, M., Spano, P. F., and Haefely, W. E., Dopamine D2 receptor stimulation decreases the inositol trisphosphate level of rat striatal slices. Eur. J. Pharmacol., 136, 263–264 (1987).

    Article  CAS  PubMed  Google Scholar 

  • Quan, W., Kim, J. H., Albert, P. R., Choi, H., and Kim, K. M., Roles of G protein and beta-arrestin in dopamine D2 receptor-mediated ERK activation. Biochem. Biophys. Res. Commun., 377, 705–709 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Robinson, S. W. and Caron, M. G., Chimeric D2/D3 dopamine receptors efficiently inhibit adenylyl cyclase in HEK 293 cells. J. Neurochem., 67, 212–219 (1996).

    Article  CAS  PubMed  Google Scholar 

  • Robinson, S. W. and Caron, M. G., Selective inhibition of adenylyl cyclase type V by the dopamine D3 receptor. Mol. Pharmacol., 52, 508–514 (1997).

    CAS  PubMed  Google Scholar 

  • Scheideler, M. A., Martin, J., Hohlweg, R., Rasmussen, J. S., Naerum, L., Ludvigsen, T. S., Larsen, P. J., Korsgaard, N., Crider, A. M., Ghosh, D., Cruse, S. F., and Fink-Jensen, A., The preferential dopamine D3 receptor agonist cis-8-OH-PBZI induces limbic Fos expression in rat brain. Eur. J. Pharmacol., 339, 261–270 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Schneider, C. S. and Mierau, J., Dopamine autoreceptor agonists: resolution and pharmacological activity of 2,6-diaminotetrahydrobenzothiazole and an aminothiazole analogue of apomorphine. J. Med. Chem., 30, 494–498 (1987).

    Article  CAS  PubMed  Google Scholar 

  • Schwartz, J. C., Levesque, D., Martres, M. P., and Sokoloff, P., Dopamine D3 receptor: basic and clinical aspects. Clin. Neuropharmacol., 16, 295–314 (1993).

    Article  CAS  PubMed  Google Scholar 

  • Seabrook, G. R., Patel, S., Marwood, R., Emms, F., Knowles, M. R., Freedman, S. B., and McAllister, G., Stable expression of human D3 dopamine receptors in GH4C1 pituitary cells. FEBS Lett., 312, 123–126 (1992).

    Article  CAS  PubMed  Google Scholar 

  • Seeman, P., Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse, 1, 133–152 (1987).

    Article  CAS  PubMed  Google Scholar 

  • Senogles, S. E., The D2s dopamine receptor stimulates phospholipase D activity: a novel signaling pathway for dopamine. Mol. Pharmacol., 58, 455–462 (2000).

    CAS  PubMed  Google Scholar 

  • Senogles, S. E., D2s dopamine receptor mediates phospholipase D and antiproliferation. Mol. Cell. Endocrinol., 209, 61–69 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Serretti, A., Macciardi, F., and Smeraldi, E., Dopamine receptor D2 Ser/Cys311 variant associated with disorganized symptomatology of schizophrenia. Schizophr. Res., 34, 207–210 (1998).

    Article  CAS  PubMed  Google Scholar 

  • Shioda, N., Yamamoto, Y., Watanabe, M., Binas, B., Owada, Y., and Fukunaga, K., Heart-type fatty acid binding protein regulates dopamine D2 receptor function in mouse brain. J. Neurosci., 30, 3146–3155 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Shpetner, H. S. and Vallee, R. B., Identification of dynamin, a novel mechanochemical enzyme that mediates interactions between microtubules. Cell, 59, 421–432 (1989).

    Article  CAS  PubMed  Google Scholar 

  • Simmonds, S. H. and Strange, P. G., Inhibition of inositol phospholipid breakdown by D2 dopamine receptors in dissociated bovine anterior pituitary cells. Neurosci. Lett., 60, 267–272 (1985).

    Article  CAS  PubMed  Google Scholar 

  • Smith, F. D., Oxford, G. S., and Milgram, S. L., Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein. J. Biol. Chem., 274, 19894–19900 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Sokoloff, P., Giros, B., Martres, M. P., Bouthenet, M. L., and Schwartz, J. C., Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature, 347, 146–151 (1990).

    Article  CAS  PubMed  Google Scholar 

  • Starr, S., Kozell, L. B., and Neve, K. A., Drug-induced upregulation of dopamine D2 receptors on cultured cells. J. Neurochem., 65, 569–577 (1995).

    Article  CAS  PubMed  Google Scholar 

  • Stemp, G., Ashmeade, T., Branch, C. L., Hadley, M. S., Hunter, A. J., Johnson, C. N., Nash, D. J., Thewlis, K. M., Vong, A. K., Austin, N. E., Jeffrey, P., Avenell, K. Y., Boyfield, I., Hagan, J. J., Middlemiss, D. N., Reavill, C., Riley, G. J., Routledge, C., and Wood, M., Design and synthesis of trans-N-[4-[2-(6-cyano-1,2,3, 4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide (SB-277011): A potent and selective dopamine D(3) receptor antagonist with high oral bioavailability and CNS pene tration in the rat. J. Med. Chem., 43, 1878–1885 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Sunahara, R. K., Niznik, H. B., Weiner, D. M., Stormann, T. M., Brann, M. R., Kennedy, J. L., Gelernter, J. E., Rozmahel, R., Yang, Y. L., Israel, Y., and et al., Human dopamine D1 receptor encoded by an intronless gene on chromosome 5. Nature, 347, 80–83 (1990).

    Article  CAS  PubMed  Google Scholar 

  • Sunahara, R. K., Guan, H. C., O’Dowd, B. F., Seeman, P., Laurier, L. G., Ng, G., George, S. R., Torchia, J., Van Tol, H. H., and Niznik, H. B., Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature, 350, 614–619 (1991).

    Article  CAS  PubMed  Google Scholar 

  • Svensson, K., Carlsson, A., Huff, R. M., Kling-Petersen, T., and Waters, N., Behavioral and neurochemical data suggest functional differences between dopamine D2 and D3 receptors. Eur. J. Pharmacol., 263, 235–243 (1994).

    Article  CAS  PubMed  Google Scholar 

  • Takei, K., Mundigl, O., Daniell, L., and De Camilli, P., The synaptic vesicle cycle: a single vesicle budding step involving clathrin and dynamin. J. Cell Biol., 133, 1237–1250 (1996).

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi, Y., Fukunaga, K., and Miyamoto, E., Activation of nuclear Ca(2+)/calmodulin-dependent protein kinase II and brain-derived neurotrophic factor gene expression by stimulation of dopamine D2 receptor in transfected NG108-15 cells. J. Neurochem., 82, 316–328 (2002a).

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi, Y., Miyamoto, E., and Fukunaga, K., Activation of the rat dopamine D2 receptor promoter by mitogenactivated protein kinase and Ca2+/calmodulin-dependent protein kinase II pathways. J. Neurochem., 83, 784–796 (2002b).

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi, Y. and Fukunaga, K., Differential subcellular localization of two dopamine D2 receptor isoforms in transfected NG108-15 cells. J. Neurochem., 85, 1064–1074 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Tang, L., Todd, R. D., and O’Malley, K. L., Dopamine D2 and D3 receptors inhibit dopamine release. J. Pharmacol. Exp. Ther., 270, 475–479 (1994).

    CAS  PubMed  Google Scholar 

  • Usiello, A., Baik, J. H., Rouge-Pont, F., Picetti, R., Dierich, A., LeMeur, M., Piazza, P. V., and Borrelli, E., Distinct functions of the two isoforms of dopamine D2 receptors. Nature, 408, 199–203 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Vallar, L., Muca, C., Magni, M., Albert, P., Bunzow, J., Meldolesi, J., and Civelli, O., Differential coupling of dopaminergic D2 receptors expressed in different cell types. Stimulation of phosphatidylinositol 4,5-bisphosphate hydrolysis in LtK-fibroblasts, hyperpolarization, and cytosolic-free Ca2+ concentration decrease in GH4C1 cells. J. Biol. Chem., 265, 10320–10326 (1990).

    CAS  PubMed  Google Scholar 

  • Van Tol, H. H., Bunzow, J. R., Guan, H. C., Sunahara, R. K., Seeman, P., Niznik, H. B., and Civelli, O., Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature, 350, 610–614 (1991).

    Article  PubMed  Google Scholar 

  • Vickery, R. G. and Von Zastrow, M., Distinct dynamin-dependent and -independent mechanisms target structurally homologous dopamine receptors to different endocytic membranes. J. Cell Biol., 144, 31–43 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Wade, T. V., Rothblat, D. S., and Schneider, J. S., Changes in striatal dopamine D3 receptor regulation during expression of and recovery from MPTP-induced parkinsonism. Brain Res., 905, 111–119 (2001).

    Article  CAS  PubMed  Google Scholar 

  • Walaas, S. I., Aswad, D. W., and Greengard, P., A dopamineand cyclic AMP-regulated phosphoprotein enriched in dopamine-innervated brain regions. Nature, 301, 69–71 (1983).

    Article  CAS  PubMed  Google Scholar 

  • Walensky, L. D., Blackshaw, S., Liao, D., Watkins, C. C., Weier, H. U., Parra, M., Huganir, R. L., Conboy, J. G., Mohandas, N., and Snyder, S. H., A novel neuron-enriched homolog of the erythrocyte membrane cytoskeletal protein 4.1. J. Neurosci., 19, 6457–6467 (1999).

    CAS  PubMed  Google Scholar 

  • Waters, N., Svensson, K., Haadsma-Svensson, S. R., Smith M. W., and Carlsson, A., The dopamine D3-receptor: a postsynaptic receptor inhibitory on rat locomotor activity. J. Neural Transm. Gen. Sect., 94, 11–19 (1993).

    Article  CAS  PubMed  Google Scholar 

  • Westrich, L. and Kuzhikandathil, E. V., The tolerance property of human D3 dopamine receptor is determined by specific amino acid residues in the second cytoplasmic loop. Biochim. Biophys. Acta, 1773, 1747–1758 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Xu, M., Koeltzow, T. E., Santiago, G. T., Moratalla, R., Cooper, D. C., Hu, X. T., White, N. M., Graybiel, A. M., White, F. J., and Tonegawa, S., Dopamine D3 receptor mutant mice exhibit increased behavioral sensitivity to concurrent stimulation of D1 and D2 receptors. Neuron, 19, 837–848 (1997).

    Article  CAS  PubMed  Google Scholar 

  • Zhang, L. J., Lachowicz, J. E., and Sibley, D. R., The D2S and D2L dopamine receptor isoforms are differentially regulated in Chinese hamster ovary cells. Mol. Pharmacol., 45, 878–889 (1994).

    CAS  PubMed  Google Scholar 

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    Dong Im Cho, Mei Zheng & Kyeong-Man Kim

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Cho, D.I., Zheng, M. & Kim, KM. Current perspectives on the selective regulation of dopamine D2 and D3 receptors. Arch. Pharm. Res. 33, 1521–1538 (2010). https://doi.org/10.1007/s12272-010-1005-8

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