Interactions of Dopamine Receptors with G Proteins

  • Susan W. Robinson
  • Marc G. Caron
Part of the The Receptors book series (REC)


Dopamine is an important neurotransmitter, playing roles in motor control, emotion and affect, neuroendocrine regulation, and regulation of sodium uptake in the kidney, among other functions. The receptors for dopamine are members of the superfamily of G protein-coupled receptors (GPCRs). To date, five mammalian dopamine receptors have been cloned (1,2)and other subtypes may await discovery. These receptors have been characterized with regard to their pharmacology and modulation of second messengers in a variety of cell types and in vivo. However, less well studied has been the intermediate step between ligand binding and second messenger regulation (i.e., interaction of the receptor with G proteins). This aspect of dopamine receptor function may be quite significant in understanding the actions of dopamine in various tissues or regions of the brain which may contain different complements of receptors and G proteins. In this chapter, we discuss the evidence for which structural features of dopamine receptors are responsible for interaction with G proteins, as well as studies examining interactions of various subtypes of dopamine receptors with specific G proteins.


Dopamine Receptor Adenylate Cyclase Agonist Binding Arachidonic Acid Release Inhibit Adenylate Cyclase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Civelli, O., Bunzow, J. R., and Grandy, D. K. (1993) Molecular diversity of the dopamine receptors. Annu. Rev. Pharmacol. Toxicol. 32, 281–307.CrossRefGoogle Scholar
  2. 2.
    Gingrich, J. A. and Caron, M. G. (1993) Recent advances in the molecular biology of dopamine receptors. Annu. Rev. Neurosci. 16, 299–321.PubMedCrossRefGoogle Scholar
  3. 3.
    Hedin, K. E., Duerson, K., and Clapham, D. E. (1993) Specificity of receptor—G protein interactions: searching for the structure behind the signal. Cell Signal. 5, 505–518.PubMedCrossRefGoogle Scholar
  4. 4.
    Savarese, T. M. and Fraser, C. M. (1992) In vitro mutagenesis and the search for structure—function relationships among G protein-coupled receptors. Biochem. J. 283, 1–19.Google Scholar
  5. 5.
    Cotecchia, S., Exum, S., Caron, M. G., and Lefkowitz, R. J. (1990) Regions of the a1-adrenergic receptor involved in coupling to phosphatidylinositol hydrolysis and enhanced sensitivity of biological function. Proc. Natl. Acad. Sci. USA 87, 2896–2900.PubMedCrossRefGoogle Scholar
  6. 6.
    Kobilka, B. K., Kobilka, T. S., Daniel, K., Regan, J. W., Caron, M. G., and Lefkowitz, R. J. (1988) Chimeric az,ß2-adrenergic receptors: delineation of domains involved in effector coupling and ligand binding specificity. Science 240, 1310–1316.PubMedCrossRefGoogle Scholar
  7. 7.
    Strader, C. D., Dixon, R. A. F., Cheung, A. H., Candelore, M. R., Blake, A. D., and Sigal, I. S. (1987) Mutations that uncouple the ß-adrenergic receptor from G, and increase agonist affinity. J. Biol. Chem. 262, 16,439–16, 443.Google Scholar
  8. 8.
    Dalman, H. M. and Neubig, R. R. (1991) Two peptides from the a2Â adrenergic receptor alter receptor G protein coupling by distinct mechanisms. J. Biol. Chem. 266, 11,025–11, 029.Google Scholar
  9. 9.
    Wess, J. Bonner, T. I., Dörje, F., and Brann, M. R. (1990) Delineation of muscarinic receptor domains conferring selectivity of coupling to guanine nucleotide-binding proteins and second messengers. Mol. Pharmacol. 38 517–523.Google Scholar
  10. 10.
    Franke, R. R., König, B., Sakmar, T. P., Khorana, H. G., and Hofmann, K. P. (1990) Rhodopsin mutants that bind but fail to activate transducin. Science 250, 123–125.Google Scholar
  11. 11.
    O’Dowd, B. F., Hnatowich, M., Regan, J. W., Leader, W. M., Caron, M. G., and Lefkowitz, R. J. (1988) Site-directed mutagenesis of the cytoplasmic domains of the human ßz-adrenergic receptor. Localization of regions involved in G protein-receptor coupling. J. Biol. Chem. 263, 15,985–15, 992.Google Scholar
  12. 12.
    Takemoto, D. J., Takemoto, L. J., Hansen, J., and Morrison, D. (1985) Regulation of retinal transducin by C-terminal peptides of rhodopsin. Biochem. J. 232, 669–672.PubMedGoogle Scholar
  13. 13.
    Schreiber, R. E., Prossnitz, E. R., Ye, R. D., Cochrane, C. G., and Bokoch, G. M. (1994) Domains of the human neutrophil N-formyl peptide receptor involved in G protein coupling. Mapping with receptor-derived peptides. J. Biol. Chem. 269, 326–331.Google Scholar
  14. 14.
    Varrault, A., Nguyen, D. L., McClue, S., Harris, B., Jouin, P., and Bockaert, J. (1994) 5-Hydroxytryptamine1A receptor synthetic peptides. Mechanisms of adenylyl cyclase inhibition. J. Biol. Chem. 269 16,720–16,725.Google Scholar
  15. 15.
    Wong, S. K.-F., Parker, E. M., and Ross, E. M. (1990) Chimeric muscarinic cholinergic: ß-adrenergic receptors that activate GS in response to muscarinic agonists. J. Biol. Chem. 265, 6219–6224.PubMedGoogle Scholar
  16. 16.
    König, B. and Grätzel, M. (1994) Site of dopamine D I receptor binding to GS protein mapped with synthetic peptides. Biochim. Biophys. Acta 1223, 261–266.PubMedCrossRefGoogle Scholar
  17. 17.
    Voss, T., Wallner, E., Czernilofsky, A. P., andFreissmuth, M. (1993) Amphipathic a-helical structure does not predict the ability of receptor-derived synthetic peptides to interact with guanine nucleotide-binding regulatory proteins. J. Biol. Chem. 268, 4637–4642.Google Scholar
  18. 18.
    Luttrell, L. M., Ostrowski, J., Cotecchia, S., Kendall, H., and Lefkowitz, R. J. (1993) Antagonism of catecholamine receptor signaling by expression of cytoplasmic domains of the receptors. Science 259, 1453–1457.PubMedCrossRefGoogle Scholar
  19. 19.
    Hawes, B. E., Luttrell, L. M., Exum, S. T., and Lefkowitz, R. J. (1994) Inhibition of G protein-coupled receptor signaling by expression of cytoplasmic domains of the receptor. J. Biol. Chem. 269, 15,776–15, 785.Google Scholar
  20. 20.
    Malek, D., Mönch, G., and Palm, D. (1993) Two sites in the third inner loop of the dopamine D2 receptor are involved in functional G protein-mediated coupling to adenylate cyclase. FEBS Lett. 325, 215–219.PubMedCrossRefGoogle Scholar
  21. 21.
    MacKenzie, R. G., Steffey, M. E., Manelli, A. M., Pollock, N. J., and Frail, D. E. (1993) A D1/D2 chimeric dopamine receptor mediates a DI response to a D2-selective agonist. FEBS Lett. 323, 59–62.PubMedCrossRefGoogle Scholar
  22. 22.
    Kozell, L. B., Machida, C. A., Neve, R. L., and Neve, K. A. (1994) Chimeric Di/D2 dopamine receptors. Distinct determinants of selective efficacy, potency, and signal transduction. J. Biol. Chem. 269 30,299–30,306.Google Scholar
  23. 23.
    McAllister, G., Knowles, M. R., Patel, S., Marwood, R., Emms, F., Seabrook, G. R., Graziano, M., Borkowski, D., Hey, P. J., and Freedman, S. B. (1993) Characterisation of a chimeric hD3/D2 dopamine receptor expressed in CHO cells. FEBS Lett. 324, 81–86.Google Scholar
  24. 24.
    Robinson, S. W., Jarvie, K. R., and Caron, M. G. (1994) High affinity agonist binding to the dopamine D3 receptor: chimeric receptors delineate a role for intracellular domains. Mol. Pharmacol. 46, 352–356.PubMedGoogle Scholar
  25. 14a.
    Robinson, S. W. and Caron, M. G. (1996) Chimeric D2/D3 dopamine receptors efficiently inhibit adenylyl cyclase in HEK 293 cells. J. Neurochem.,in press.Google Scholar
  26. 25.
    Boundy, V. A., Luedtke, R. R., and Molinoff, P. B. (1993) Development of polyclonal anti-D2 dopamine receptor antibodies to fusion proteins: inhibition of D2 receptor-G protein interaction. J. Neurochem. 60, 2181–2191.PubMedCrossRefGoogle Scholar
  27. 26.
    Plug, M. J., Dijk, J., Maassen, A., and Möller, W. (1992) An anti-peptide antibody that recognizes the dopamine D, receptor from bovine striatum. Eur. J. Biochem. 206, 123–130.PubMedCrossRefGoogle Scholar
  28. 27.
    Boundy, V. A., Luedtke, R. R., Artymyshyn, R. P., Filtz, T. M., and Molinoff, P. B. (1993) Development of polyclonal anti-D2 dopamine receptor antibodies using sequence-specific peptides. Mol. Pharmacol. 43, 666–676.Google Scholar
  29. 28.
    Chazot, P. L., Doherty, A. J., and Strange, P. G. (1993) Antisera specific for D2 dopamine receptors. Biochem. J. 289, 789–794.PubMedGoogle Scholar
  30. 29.
    Pollock, N. J. Manelli, A. M., Hutchins, C. W., Steffey, M. E., MacKenzie, R. G., and Frail, D. E. (1992) Serine mutations in transmembrane V of the dopamine D1 receptor affect ligand interactions and receptor activation. J. Biol. Chem. 267 17,780–17,786.Google Scholar
  31. 30.
    Neve, K. A., Cox, B. A., Henningsen, R. A., Spanoyannis, A., and Neve, R. L. (1991) Pivotal role for aspartate-80 in the regulation of dopamine D2 receptor affinity for drugs and inhibition of adenylyl cyclase. Mol. Pharmacol. 39, 733–739.PubMedGoogle Scholar
  32. 31.
    Tiberi, M. and Caron, M. G. (1994) High agonist-independent activity is a distinguishing feature of the dopamine DIB receptor subtype. J. Biol. Chem. 269, 27,925–27, 931.Google Scholar
  33. 32.
    Demchyshyn, L. L., Sugamori, K. S., Lee, F. J. S., Hamadanizadeh, S. A., and Niznik, H. B. (1995) The dopamine DID receptor. Cloning and characterization of three pharmacologically distinct D1-like receptors from Gallus domesticus. J. Biol. Chem. 270, 4005–4012.Google Scholar
  34. 33.
    Sugamori, K. S., Demchyshyn, L. L., Chung, M., and Niznik, H. B. (1994) DIA, D I B, and Dig dopamine receptors from Xenopus laevis. Proc. Natl. Acad. Sci. USA 91, 10,536–10, 540.Google Scholar
  35. 34.
    Liu, Y. F., Civelli, O., Zhou, Q.-Y., and Albert, P. R. (1992) Cholera toxin-sensitive 3’5’-cyclic adenosine monophosphate and calcium signals of the human dopamine-D1 receptor: selective potentiation by protein kinase A. Mol. Endocrinol. 6, 1815–1824.PubMedCrossRefGoogle Scholar
  36. 35.
    Frail, D. E., Manelli, A. M., Witte, D. G., Lin, C. W., Steffey, M. E., and MacKenzie, R. G. (1993) Cloning and characterization of a truncated dopamine DI receptor from goldfish retina: stimulation of cyclic AMP production and calcium mobilization. Mol. Pharmacol. 44, 1113–1118.PubMedGoogle Scholar
  37. 36.
    Rodrigues, P. S. and Dowling, J. E. (1990) Dopamine induces neurite retraction in retinal horizontal cells via diacylglycerol and protein kinase C. Proc. Natl. Acad. Sci. USA 87, 9693–9697.CrossRefGoogle Scholar
  38. 37.
    Pedersen, U. B., Norby, B., Jensen, A. A., Schiedt, M., Hansen, A., Suhr-Jessen, P., Scheideler, M., Thastrup, O., and Andersen, P. H. (1994) Characteristics of stably expressed human Di. and Dib receptors: atypical behavior of the dopamine DBb receptor. Eur. J. Pharmacol. 267, 85–93.PubMedCrossRefGoogle Scholar
  39. 38.
    Undie, A. S. and Friedman, E. (1990) Stimulation of a dopamine Di receptor enhances inositol phosphates formation in rat brain. J. Pharmacol. Exp. Ther. 253, 987–992.PubMedGoogle Scholar
  40. 39.
    Undie, A. S., Weinstock, J., Sarau, H. M., and Friedman, E. (1994) Evidence for a distinct Di-like dopamine receptor that couples to activation of phosphoinositide metabolism in brain. J Neurochem. 62, 2045–2048.PubMedCrossRefGoogle Scholar
  41. 40.
    Felder, C. C., Campbell, T., Albrecht, F., and Jose, P. A. (1990) Dopamine inhibits Na`—H+ exchanger activity in renal BBMV by stimulation of adenylate cyclase. Am. J. Physiol. 259, F297 — F303.PubMedGoogle Scholar
  42. 41.
    Felder, C. C., Albrecht, F. E., Campbell, T., Eisner, G. M., and Jose, P. A. (1993) cAMP-independent, G protein-linked inhibition of Na’/H’ exchange in renal brush border by D, dopamine agonists. Am. J. Physiol. 264, F1032 — F1037.Google Scholar
  43. 42.
    Laitinen, J. T. (1993) Dopamine stimulates K’ efflux in the chick retina via Di receptors independently of adenylyl cyclase activation. J. Neurochem. 61, 1461–1469.PubMedCrossRefGoogle Scholar
  44. 43.
    Kebabian, J. W. and Calne, D. B. (1979) Multiple receptors for dopamine. Nature 277, 93–96.PubMedCrossRefGoogle Scholar
  45. 44.
    Hayes, G., Biden, T. J., Selbie, L. A., and Shine, J. (1992) Structural subtypes of the dopamine D, receptor are functionally distinct: expression of the cloned D,A and D2B subtypes in a heterologous cell line. Mol. Endocrinol. 6, 920–926.PubMedCrossRefGoogle Scholar
  46. 45.
    Montmayeur, J.-P. and Borrelli, E. (1991) Transcription mediated by a cAMPresponsive promoter element is reduced upon activation of dopamine D2 receptors. Proc. Natl. Acad. Sci. USA 88, 3135–3139.PubMedCrossRefGoogle Scholar
  47. 46.
    Montmayeur, J.-P., Guiramand, J., and Borrelli, E. (1993) Preferential coupling between dopamine D2 receptors and G-proteins. Mol. Endocrinol. 7, 161–170.PubMedCrossRefGoogle Scholar
  48. 47.
    Felder, C. C., Williams, H. L., and Axelrod, J. (1991) A transduction pathway associated with receptors coupled to the inhibitory guanine nucleotide binding protein G, that amplifies ATP-mediated arachidonic acid release. Proc. Natl. Acad. Sci. USA 88, 6477–6480.PubMedCrossRefGoogle Scholar
  49. 48.
    Kanterman, R. Y., Mahan, L. C., Briley, E. M., Monsma, F. J., Sibley, D. R., Axelrod, J., and Felder, C. C. (1991) Transfected D, dopamine receptors mediate the potentiation of arachidonic acid release in Chinese hamster ovary cells. Mol. Pharmacol. 39, 364–369.PubMedGoogle Scholar
  50. 49.
    Piomelli, D. Pilon, C., Giros, B., Sokoloff, P., Martres, M.-P., and Schwartz, J.-C. (1991) Dopamine activation of the arachidonic acid cascade as a basis for D,/D2 synergism. Nature 353 164–167.Google Scholar
  51. 50.
    Liu, Y. F., Civelli, O., Grandy, D. K., and Albert, P. R. (1992) Differential sensitivity of the short and long human dopamine D2 receptor subtypes to protein kinase C. J. Neurochem. 59, 2311–2317.PubMedCrossRefGoogle Scholar
  52. 51.
    Vallar, L., Muca, C., Magni, M., Albert, P., Bunzow, J., Meldolesi, J., and Civelli, O. (1990) Differential coupling of dopaminergic D2 receptors expressed in different cell types. Stimulation ofphosphatidylinosito14,5-bisphosphate hydrolysis in Ltic fibroblasts, hyperpolarization, and cytosolic-free Cat’ concentration decrease in GH4C, cells. J. Biol. Chem. 265, 10,320–10, 326.Google Scholar
  53. 52.
    MacKenzie, R. G., VanLeeuwen, D., Pugsley, T. A., Shih, Y.-H., Demattos, S., Tang, L., Todd, R. D., and O’Malley, K. L. (1994) Characterization of the human dopamine D3 receptor expressed in transfected cell lines. Eur. J. Pharmacol. 266, 79–85.PubMedCrossRefGoogle Scholar
  54. 53.
    Tang, L., Todd, R. D., Heller, A., and O’Malley, K. L. (1994) Pharmacological and functional characterization of D2, D3 and D4 dopamine receptors in fibroblast and dopaminergic cell lines. J. Pharmacol. Exp. Ther. 268, 495–502.PubMedGoogle Scholar
  55. 54.
    Freedman, S. B., Patel, S., Marwood, R., Emms, F., Seabrook, G. R., Knowles, M. R., and McAllister, G. (1994) Expression andpharmacological characterization of the human D3 dopamine receptor. J. Pharmacol. Exp. Ther. 268, 417–426.PubMedGoogle Scholar
  56. 55.
    Nussinovitch, I. and Kleinhaus, A. L. (1992) Dopamine inhibits voltage-activated calcium channel currents in rat pars intermedia pituitary cells. Brain Res. 574, 49–55.PubMedCrossRefGoogle Scholar
  57. 56.
    Liu, Y. F., Jakobs, K. H. Rasenick, M. M., and Albert, P. R. (1994) G protein specificity in receptor-effector coupling. Analysis of the roles of Go and G.2 in GH4C, pituitary cells. J. Biol. Chem. 269 13,880–13,886.Google Scholar
  58. 57.
    Seabrook, G. R., Knowles, M., Brown, N., Myers, J., Sinclair, H., Patel, S., Freedman, S. B., and McAllister, G. (1994) Pharmacology of high-threshold calcium currents in GH4C 1 pituitary cells and their regulation by activation of human D2 and D4 dopamine receptors. Br. J. Pharmacol. 112, 728–734.PubMedCrossRefGoogle Scholar
  59. 58.
    Seabrook, G. R., McAllister, G., Knowles, M. R., Myers, J., Sinclair, H., Patel, S., Freedman, S. B., and Kemp, J. A. (1994) Depression of high-threshold calcium currents by activation of human D2 (short) dopamine receptors expressed in differentiated NG108–15 cells. Br. J. Pharmacol. 111, 1061–1066.PubMedCrossRefGoogle Scholar
  60. 59.
    Einhorn, L. C., Gregerson, K. A., and Oxford, G. S. (1991) D2 dopamine receptor activation of potassium channels in identified rat lactotrophs: whole-cell and single-channel recording. J. Neurosci. 11, 3727–3737.PubMedGoogle Scholar
  61. 60.
    Memo, M., Pizzi, M., Belloni, M., Benarese, M., and Spano, P. F. (1992) Activation of dopamine D2 receptors linked to voltage-sensitive potassium channels reduces forskolin-induced cyclic AMP formation in rat pituitary cells. J. Neurochem. 59, 1829–1835.PubMedCrossRefGoogle Scholar
  62. 61.
    Baertschi, A. J., Audigier, Y., Lledo, P.-M., Israel, J.-M., Bockaert, J., and Vincent, J.-D. (1992) Dialysis of lactotropes with antisense oligonucleotides assigns guanine nucleotide binding protein subtypes to their channel effectors. Mol. Endocrinol. 6, 2257–2265.Google Scholar
  63. 62.
    Lledo, P. M., Homburger, V., Bockaert, J., and Vincent, J.-D. (1992) Differential G protein-mediated coupling of D2 dopamine receptors to K+ and Cat+ currents in rat anterior pituitary cells. Neuron 8, 455–463.PubMedCrossRefGoogle Scholar
  64. 63.
    Castellano, M. A., Liu, L.-X., Monsma, F. J., Sibley, D. R., Kapatos, G., and Chiodo, L. A. (1993) Transfected D2 short dopamine receptors inhibit voltage-dependent potassium current in neuroblastoma x glioma hybrid (NG108–15) cells. Mol. Pharmacol. 44, 649–656.PubMedGoogle Scholar
  65. 64.
    Tang, L., Todd, R. D., and O’Malley, K. L. (1994) Dopamine D2 and D3 receptors inhibit dopamine release. J. Pharmacol. Exp. Ther. 270, 475–479.PubMedGoogle Scholar
  66. 65.
    Neve, K. A., Kozlowski, M. R., and Rosser, M. P. (1992) Dopamine D2 receptor stimulation of Na+/H+ exchange assessed by quantification of extracellular acidification. J. Biol. Chem. 267, 25,748–25, 753.Google Scholar
  67. 66.
    Ganz, M. B., Pachter, J. A., and Barber, D. L. (1990) Multiple receptors coupled to adenylate cyclase regulate Na-H exchange independent ofcAMP. J. Biol. Chem. 265, 8989–8992.PubMedGoogle Scholar
  68. 67.
    Chio, C. L., Lajiness, M. E., and Huff, R. M. (1994) Activation of heterologously expressed D3 dopamine receptors: comparison with D2 dopamine receptors. Mol. Pharmacol. 45, 51–60.PubMedGoogle Scholar
  69. 68.
    Florio, T. Pan, M.-G., Newman, B., Hershberger, R. E., Civelli, O., and Stork, P. J. S. (1992) Dopaminergic inhibition of DNA synthesis in pituitary tumor cells is associated with phosphotyrosine phosphatase activity. J. Biol. Chem. 267 24,169–24,172.Google Scholar
  70. 69.
    Senogles, S. E. (1994) The D2 dopamine receptor mediates inhibition of growth in GH4ZR, cells: involvement of protein kinase-Ce. Endocrinology 134, 783–789.PubMedCrossRefGoogle Scholar
  71. 70.
    Lajiness, M. E., Chio, C. L., and Huff, R. M. (1993) D2 dopamine receptor stimulation of mitogenesis in transfected Chinese hamster ovary cells: relationship to dopamine stimulation of tyrosine phosphorylations. J. Pharmacol. Exp. Ther. 267, 1573–1581.PubMedGoogle Scholar
  72. 71.
    Swarzenski, B. C., Tang, L., Oh, Y. J., O’Malley, K. L., and Todd, R. D. (1994) Morphogenic potentials of D2, D3, and D4 dopamine receptors revealed in transfected neuronal cell lines. Proc. Natl. Acad. Sci. USA 91, 649–653.PubMedCrossRefGoogle Scholar
  73. 72.
    Giros, B., Martres, M.-P., Sokoloff, P., and Schwartz, J.-C. (1990) Clonage du gène du récepteur dopaminergique D3 humain et identification de son chromosome. C. R. Acad. Sci. 311, 501–508.Google Scholar
  74. 73.
    Sokoloff, P., Giros, B., Martres, M.-P., Bouthenet, M.-L., and Schwartz, J.-C. (1990) Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 347, 146–151.PubMedCrossRefGoogle Scholar
  75. 74.
    Boundy, V. A., Luedtke, R. R., Gallitano, A. L., Smith, J. E., Filtz, T. M., Kallen, R. G., and Molinoff, P. B. (1993) Expression and characterization of the rat D3 dopamine receptor: pharmacologic properties and development of antibodies. J. Pharmacol. Exp. Ther. 264, 1002–1011.PubMedGoogle Scholar
  76. 75.
    McAllister, G., Knowles, M. R., Ward-Booth, S. M., Sinclair, H. A., Patel, S., Marwood, R., Emms, F., Patel, S., Seabrook, G. R., and Freedman, S. B. (1995) Functional coupling of human D2, D3, and D, dopamine receptors in HEK293 cells. J. Receptor Signal Trans. Res. 15, 267–281.CrossRefGoogle Scholar
  77. 76.
    Lévesque, D., Diaz, J., Pilon, C., Martres, M.-P., Giros, B., Souil, E., Schott, D., Morgat, J.-L., Schwartz, J.-C., and Sokoloff, P. (1992) Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxyN,N-di-n-propyl-2-aminotetralin. Proc. Natl. Acad. Sci. USA 89, 8155–8159.PubMedCrossRefGoogle Scholar
  78. 77.
    Castro, S. W. and Strange, P. G. (1993) Coupling of D2 and D3 dopamine receptors to G-proteins. FEBS Lett. 315, 223–226.PubMedCrossRefGoogle Scholar
  79. 78.
    Seabrook, G. R., Patel, S., Marwood, R., Emms, F., Knowles, M. R., Freedman, S. B., and McAllister, G. (1992) Stable expression of human D3 dopamine receptors in GH4C, pituitary cells. FEBS Lett. 312, 123–126.PubMedCrossRefGoogle Scholar
  80. 79.
    Pilon, C., Lévesque, D., Dimitriadou, V., Griffon, N., Martres, M.-P., Schwartz, J.-C., and Sokoloff, P. (1994) 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.PubMedCrossRefGoogle Scholar
  81. 80.
    Potenza, M. N., Graminski, G. F., Schmauss, C., and Lerner, M. R. (1994) Functional expression and characterization of human D2 and D3 dopamine receptors. J. Neurosci. 14, 1463–1476.PubMedGoogle Scholar
  82. 81.
    Seabrook, G. R., Kemp, J. A., Freedman, S. B., Patel, S., Sinclair, H. A., and McAllister, G. (1994) Functional expression of human D3 dopamine receptors in differentiated neuroblastoma x glioma NG108–15 cells. Br. J. Pharmacol. 111, 391–393.PubMedCrossRefGoogle Scholar
  83. 82.
    Cohen, A. I., Todd, R. D., Harmon, S., and O’Malley, K. L. (1992) Photoreceptors of mouse retinas possess D4 receptors coupled to adenylate cyclase. Proc. Natl. Acad. Sci. USA 89, 12,093–12, 097.Google Scholar
  84. 83.
    Mills, A., Allet, B., Bernard, A., Chabert, C., Brandt, E., Cavegn, C., Chollet, A., and Kawashima, E. (1993) Expression and characterization of human D4 dopamine receptors in baculovirus-infected cells. FEBS Lett. 320, 130–134.PubMedCrossRefGoogle Scholar
  85. 84.
    Asghari, V., Schoots, O., Van Kats, S., Ohara, K., Jovanovic, V., Guan, H.-C., Bunzow, J. R., Petronis, A., and Van Tol, H. H. M. (1994) Dopamine D4 receptor repeat: analysis of different native and mutant forms of the human and rat genes. Mol. Pharmacol. 46, 364–373.PubMedGoogle Scholar
  86. 85.
    McHale, M., Coldwell, M. C., Herrity, N., Boyfield, I., Winn, F.M., Ball, S., Cook, T., Robinson, J. H., and Gloger, I. S. (1994) Expression and functional characterisation of a synthetic version of the human D4 dopamine receptor in a stable human cell line. FEBS Lett. 345, 147–150.Google Scholar
  87. 86.
    Chio, C. L., Drong, R. F., Riley, D. T., Gill, G. S., Slightom, J. L., and Huff, R. M. (1994) D4 dopamine receptor-mediated signaling events determined in transfected Chinese hamster ovary cells. J. Biol. Chem. 269, 11,813–11, 819.Google Scholar
  88. 87.
    Neer, E. J. (1995) Heterotrimeric G proteins: organizers of transmembrane signals. Cell 80, 249–257.PubMedCrossRefGoogle Scholar
  89. 88.
    Missale, C., Boroni, F., Castelletti, L. Dal Toso, R., Gabellini, N., Sigala, S., and Spano, P. F. (1991) Lack of coupling of D-2 receptors to adenylate cyclase in GH-3 cells exposed to epidermal growth factor. Possible role of a differential expression of G, protein subtypes. J. Biol. Chem. 266 23,392–23,398.Google Scholar
  90. 89.
    Missale, C., Boroni, F., Sigala, S., Castelletti, L., Falardeau, P., Dal Toso, R., Caron, M. G., and Spano, P. F. (1994) Epidermal growth factor promotes uncoupling from adenylyl cyclase of the rat Des receptor expressed in GH,C, cells. J. Neurochem. 62, 907–915.PubMedCrossRefGoogle Scholar
  91. 90.
    Bouvier, C., Forget, H., Lagacé, G., Drews, R., Sinnett, D., Labuda, D., and Collu, R. (1991) G proteins in normal rat pituitaries and in prolactin-secreting rat pituitary tumors. Mol. Cell Endocrinol. 78, 33–44.Google Scholar
  92. 91.
    Lew, A. M., Yao, H., and Elsholtz, H. P. (1994) G1a2- and Goa mediated signaling in the Pit-l-dependent inhibition of the prolactin gene promoter. Control of transcription by dopamine D2 receptors. J. Biol. Chem. 269, 12,007–12, 013.Google Scholar
  93. 92.
    Senogles, S. E. (1994) The D2 dopamine receptor isoforms signal through distinct Gia proteins to inhibit adenylyl cyclase. A study with site-directed mutant Gia proteins. J. Biol. Chem. 269, 23,120–23, 127.Google Scholar
  94. 93.
    Conklin, B. R. and Bourne, H. R. (1993) Structural elements of Ga subunits that interact with Gßy, receptors and effectors. Cell 73, 631–641.PubMedCrossRefGoogle Scholar
  95. 94.
    Conklin, B. R., Farfel, Z., Lustig, K. D., Julius, D., and Bourne, H. R. (1993) Substitution of three amino acids switches receptor specificity of Gqa to that of G. Nature 363, 274–276.PubMedCrossRefGoogle Scholar
  96. 95.
    Voyno-Yasenetskaya, T., Conklin, B. R., Gilbert, R. L., Hooley, R., Bourne, H. R., and Barber, D. L. (1994) Ga 13 stimulates Na-H exchange. J. Biol. Chem. 269, 4721–4724.PubMedGoogle Scholar
  97. 96.
    Wong, Y. H., Conklin, B. R., and Bourne, H. R. (1992) Gz-mediated hormonal inhibition of cyclic AMP accumulation. Science 255, 339–342.PubMedCrossRefGoogle Scholar
  98. 97.
    Plug, M. J., Möller, W., and Dijk, J. (1992) Interactions between the dopamine D2 receptor and GTP-binding proteins. Biochem. Int. 28, 21–29.PubMedGoogle Scholar
  99. 98.
    Senogles, S. E., Spiegel, A. M., Padrell, E., Iyengar, R., and Caron, M. G. (1990) Specificity ofreceptor-G protein interactions. Discrimination of G subtypes by the D2 dopamine receptor in a reconstituted system. J. Biol. Chem. 265, 4507–4514.PubMedGoogle Scholar
  100. 99.
    Friedman, E., Butkerait, P., and Wang, H.-Y. (1993) Analysis of receptor-stimulated and basal guanine nucleotide binding to membrane G proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Anal. Biochem. 214, 171–178.PubMedCrossRefGoogle Scholar
  101. 100.
    Clapham, D. E. and Neer, E. J. (1993) New roles for G-protein ßy-dimers in trans-membrane signalling. Nature 365, 403–406.PubMedCrossRefGoogle Scholar
  102. 101.
    Federman, A. D., Conklin, B. R., Schrader, K. A., Reed, R. R., and Bourne, H. R. (1992) Hormonal stimulation of adenylyl cyclase through Gi-protein 07 subunits. Nature 356, 159–161.Google Scholar
  103. 102.
    Tang, W.-J. and Gilman, A. G. (1991) Type-specific regulation of adenylyl cyclase by G protein 13y subunits. Science 254, 1500–1503.PubMedCrossRefGoogle Scholar
  104. 103.
    Lustig, K. D., Conklin, B. R., Herzmark, P., Taussig, R., and Bourne, H. R. (1993) Type II adenylylcyclase integrates coincident signals from Gç, G., and Gq. J. Biol. Chem. 268, 13,900–13, 905.Google Scholar
  105. 104.
    Faure, M., Voyno-Yasenetskaya, T. A., and Bourne, H. R. (1994) cAMP and ßy subunits of heterotrimeric G proteins stimulate the mitogen-activated protein kinase pathway in COS-7 cells. J. Biol. Chem. 269, 7851–7854.Google Scholar
  106. 105.
    Kleuss, C., Scherübl, H., Hescheler, J., Schultz, G., and Wittig, B. (1992) Different 13-subunits determine G-protein interaction with transmembrane receptors. Nature 358, 424–426.PubMedCrossRefGoogle Scholar
  107. 106.
    Kleuss, C., Scherübl, H., Hescheler, J., Schultz, G., and Wittig, B. (1993) Selectivity in signal transduction determined by y subunits of heterotrimeric G proteins. Science 259, 832–834.PubMedCrossRefGoogle Scholar
  108. 107.
    de la Pena, P., del Camino, D., Pardo, L. A., Dominguez, P., and Barros, F. (1995) Gs couples thyrotropin-releasing hormone receptors expressed inXenopus oocytes to phospholipase C. J. Biol. Chem. 270, 3554–3559.PubMedCrossRefGoogle Scholar
  109. 108.
    Hervé, D. Lévi-Strauss, M., Marey-Semper, I. Verney, C., Tassin, J.-P., Glowinski, J., and Girault, J.-A. (1993) Golf. and Gs in rat basal ganglia: possible involvement of Go if in the coupling of dopamine DI receptor with adenylyl cyclase. J. Neurosci. 13,2237–2248.Google Scholar
  110. 109.
    DiMarzo, V., Vial, D., Sokoloff, P., Schwartz, J.-C., and Piomelli, D. (1993) Selection of alternative g-mediated signaling pathways at the dopamine D2 receptor by protein kinase C. J. Neurosci. 13, 4846–4853.Google Scholar
  111. 110.
    Seeman, P. (1987) Dopamine receptors in human brain diseases, in Receptor Biochemistry and Methodology, vol. 8: Dopamine Receptors ( Creese, I. and Fraser, C. M., eds.), Liss, New York, pp. 233–245.Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Susan W. Robinson
  • Marc G. Caron

There are no affiliations available

Personalised recommendations