Signaling Pathways Modulated by Dopamine Receptors

  • Rita M. Huff
Part of the The Receptors book series (REC)


Knowledge of the intracellular signaling events altered by the binding of dopamine to its receptors is critical to the understanding of how dopamine and dopaminergic drugs elicit their actions. Activation of a signal transduction mechanism that can regulate ion channels and turn on second messenger systems is the first step toward a variety of responses in neurons, from immediate changes in neuron excitability to long-term modulatory processes. Dopamine is a neurotransmitter and, thus, affects the excitability of neurons, but it also regulates protein kinases and transcription factors through signal transduction cascades initiated by the receptors. The long-term adaptive responses resulting from dopamine receptor activation or blockade are undoubtedly important for the effects of psychotropic drugs (1). Characterization of the initial events triggered by activation of dopamine receptors at a molecular level can contribute to an understanding of how changes in ion channel actuation, protein phosphorylation, and the genetic programs of the cells can occur.


Dopamine Receptor Adenylate Cyclase Pituitary Cell Pertussis Toxin Arachidonic Acid Release 
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  1. 1.
    Duman, R. S., Heninger, G. R., and Nestler, E. J. (1994) Molecular psychiatry, adaptations of receptor-coupled signal transduction pathways underlying stress-and drug-induced neural plasticity. J. Nervous Mental Dis 182, 692–700.CrossRefGoogle Scholar
  2. 2.
    Hepler, J. R. and Gilman, A. G. (1992) G proteins. Trends Biochem. Sci 17, 383–387.PubMedCrossRefGoogle Scholar
  3. 3.
    Sternweis, P. C. (1994) The active role of ßy in signal transduction. Curr. Opin. Cell Biol 6, 198–203.PubMedCrossRefGoogle Scholar
  4. 4.
    Lange-Carter, C. A., Pleiman, C. M., Gardner, A. M., Blumer, K. J., and Johnson, G. L. (1993) A divergence in the MAP kinase regulatory network defined by MEK kinase and raf. Science 260, 315–319.PubMedCrossRefGoogle Scholar
  5. 5.
    Limbird, L. (1988) Receptors linked to inhibition of adenylate cyclase: additional signalling mechanisms. FASEB J. 2, 2686–2695.PubMedGoogle Scholar
  6. 6.
    Milligan, G. (1993) Mechanisms of multifunctional signalling by G protein-linked receptors. Trends Pharmacol. Sci 14, 239–244.PubMedCrossRefGoogle Scholar
  7. 7.
    Iyenger, R. (1993) Molecular and functional diversity of mammalian Gs-stimulated adenylyl cyclases. FASEB J. 7, 768–775.Google Scholar
  8. 8.
    Tang, W.-J. and Gilman, A. G. (1992) Adenylyl cyclases. Cell 70, 869–872.PubMedCrossRefGoogle Scholar
  9. 9.
    Taussig, R., Iniguez-Lluhi, J. A., and Gilman, A. G. (1993) Inhibition of adenylyl cyclase by G.. Science 261, 218–221.PubMedCrossRefGoogle Scholar
  10. 10.
    Lustig, K. D., Conklin, B. R., Herzmark, P Taussig, R., and Boume, H. R. (1993) Type II adenylylcyclase integrates coincident signals from G5, Gi, and Gq. J. Biol. Chem 268 13,900–13,905.Google Scholar
  11. 11.
    Anholt, R. R. H. (1994) Signal integration in the nervous system: adenylate cyclases as molecular coincidence detectors. Trends Neurosci. 17, 37–41.PubMedCrossRefGoogle Scholar
  12. 12.
    Kebabian, J. W. and Calne, D. B. (1979) Multiple receptors for dopamine. Nature 277, 93–96.PubMedCrossRefGoogle Scholar
  13. 13.
    De Camilli, P., Macconi, D., and Spada, A. (1979) Dopamine inhibits adenylate cyclase in human prolactin-secreting pituitary adenomas. Nature 278, 252–254.PubMedCrossRefGoogle Scholar
  14. 14.
    Sibley, D. R. and Monsma, F. J., Jr. (1992) Molecular biology of dopamine receptors. Trends Pharmacol. Sci 13, 61–69.PubMedCrossRefGoogle Scholar
  15. 15.
    Vallar, L. and Meldolesi, J. (1989) Mechanisms of signal transduction at the dopamine D2 receptor. Trends Pharmacol. Sci 10, 74–77.PubMedCrossRefGoogle Scholar
  16. 16.
    Vallar, L., Muca, C., Magni, M., Albert, P., Bunzow, J., Meldolesi, J., and Civelli, O. (1990) Differential coupling ofdopaminergic D2 receptors expressed in different cell types. J. Biol. Chem. 265, 10,320–10, 326.Google Scholar
  17. 17.
    Nerve, D., Levi-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 Golf in the coupling of dopamine D1 receptor with adenylyl cyclase. J. Neurosci 13, 2237–2248.Google Scholar
  18. 18.
    Kebabian, J W., Petzold, G. L., and Greengard, P. (1972) Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain and its similarity to the “dopamine receptor.” Proc. Natl. Acad. Sci. USA 69 2145–2149.Google Scholar
  19. 19.
    Hemmings, H. C., Jr., Walaas, S. I., Ouimet, C. C., and Greengard, P. (1987) Dopaminergic regulation of protein phosphorylation in the striatum: DARPP-32. Trends Neurosci. 10, 377–383.CrossRefGoogle Scholar
  20. 20.
    Hemmings, H. C., Jr., Greengard, P., Tung, H. Y. L., and Cohen, P. (1984) DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1. Nature 310, 503–505.PubMedCrossRefGoogle Scholar
  21. 21.
    Halpain, S., Girault, J.-A., and Greengard, P. (1990) Activation of NMDA receptors induces dephosphorylation of DARPP-32 in rat striatal slices. Nature 343, 369–372.PubMedCrossRefGoogle Scholar
  22. 22.
    Snyder, G. L., Fisone, G., and Greengard, P. (1994) Phosphorylation of DARPP-32 is regulated by GABA in rat striatum and substantia nigra. J. Neurochem 63, 1766–1771.PubMedCrossRefGoogle Scholar
  23. 23.
    Schinelli, S., Paolillo, M., and Corona, G. L. (1994) Opposing actions of D1- and D2-receptors on arachidonic acid release and cyclic AMP production in striatal neurons. J. Neurochem 62, 944–949.PubMedCrossRefGoogle Scholar
  24. 24.
    Piomelli, D. and Greengard, P. (1990) Lipoxygenase metabolites of arachidonic acid in neuronal transmembrane signalling. Trends Pharmacol. Sci 11, 367–373.PubMedCrossRefGoogle Scholar
  25. 25.
    Fazeli, M. S. (1992) Synaptic plasticity: on the trail of the retrograde messenger. Trends Neurosci 15 115–117 Google Scholar
  26. 26.
    Undie, A. S. and Friedman, E. (1990) Stimulation of a dopamine D1 receptor enhances inositol phosphates formation in rat brain. J. Pharmacol. Exp. Ther 253, 987–992.PubMedGoogle Scholar
  27. 27.
    Undie, A. S., Weinstock, J., Sarau, H. M., and Friedman, E. (1994) Evidence for a distinct D1-like dopamine receptor that couples to activation of phosphoinositide metabolism in brain. J. Neurochem 62, 2045–2048.PubMedCrossRefGoogle Scholar
  28. 28.
    Sidhu, A. and Fishman, P. H. (1990) Identification and characterization of functional D1 dopamine receptors in a human neuroblastoma cell line. Biochem. Biophys. Res. Commun 166, 574–579.PubMedCrossRefGoogle Scholar
  29. 29.
    Monsma F. J., Jr., Brassard, D. L., and Sibley, D. R. (1989) Identification and characterization of Dl and D2 dopamine receptors in cultured neuroblastoma and retinoblastoma clonal cell lines. Brain Res. 492, 314–324.PubMedCrossRefGoogle Scholar
  30. 30.
    Barton, A. C. and Sibley, D. R. (1990) Agonist-induced desensitization of D, dopamine receptors linked to adenylyl cyclase activity in cultured NS20Y neuroblastoma cells. Mol. Pharmacol 38, 531–541.PubMedGoogle Scholar
  31. 31.
    Lovenberg, T. W., Roth, R. H., Nichols, D. E., and Mailman, R. B. (1991) D, dopamine receptors of NS20Y neuroblastoma cells are functionally similar to rat striatal D, receptors. J. Neurochem 57, 1563–1569.Google Scholar
  32. 32.
    Nash, S. R., Godinot, N., and Caron, M. G. (1993) Cloning and characterization of the opossum kidney cell D1 dopamine receptor: expression of identical D1A and Dl B dopamine receptor mRNAs in opossum kidney and brain. Mol. Pharmacol 44, 918–925.PubMedGoogle Scholar
  33. 33.
    Zhou, Q.-Y., Grandy, D. K., Thambi, L., Kushner, J. A., Van Tol, H. H. M., Cone, R., Pribnow, D., Salon, J., Bunzow, J. R., and Civelli, O. (1990) Cloning and expression of human and rat D, dopamine receptors. Nature 347, 76–80.Google Scholar
  34. 34.
    Dearry, A., Gingrich, J. A., Falardeau, P., Fremeau, R. T., Jr., Bates, M. D., and Caron, M. G. (1990) Molecular cloning and expression of the gene for a human D, dopamine receptor. Nature 347, 72–75.PubMedCrossRefGoogle Scholar
  35. 35.
    Monsma, F. J., Jr., Mahan, L. C., McVittie, L. D., Gerfen, C. R., and Sibley, D. R. (1990) Molecular cloning and expression of a D, dopamine receptor linked to adenylyl cyclase activation. Proc. Natl. Acad. Sci. USA 87, 6723–6727.PubMedCrossRefGoogle Scholar
  36. 36.
    Pedersen, U. B., Norby, B., Jensen, A. A., Schiodt, M., Hansen, A., Suhr-Jessen, P., Scheideler, M., Thastrup, O., and Andersen, P. H. (1994) Characteristics of stably expressed human dopamine Dia and Dib receptors: atypical behavior of the dopamine Dib receptor. Eur. J. Pharmacol 267, 85–93.PubMedCrossRefGoogle Scholar
  37. 37.
    Tiberi, M., Jarvie, K. R., Silvie, C., Falardeau, P., Gingrich, J. A., Godinot, N., Bertrand, L., Yang-Feng, T. L., Fremeau, R. T., and Caron, M. G. (1991) Cloning, molecular characterization, and chromosomal assignment of a gene encoding a second D1 dopamine receptor subtype: differential expression pattern in rat brain compared with the D1A receptor. Proc. Natl. Acad. Sci. USA 88, 7491–7495.PubMedCrossRefGoogle Scholar
  38. 38.
    Weinshank, R. L., Adhan, N., Macchi, M., Olsen, M. A., Branchek, T. A., and Hartig, P. R. (1991). Molecular cloning and characterization of a high affinity dopamine receptor (D1 beta) and its pseudogene. J. Biol. Chem. 266, 22,427–22, 435.Google Scholar
  39. 39.
    Grandy, D. K., Zhang, Y., Bouvier, C., Zhou, Q.-Y., Johnson, R. A., Allen, L., Buck, K., Bunzow, J. R., Salon, J., and Civelli, O. (1991) Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes. Proc. Natl. Acad. Sci. USA 88, 9175–9179.Google Scholar
  40. 40.
    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. M., and Niznik, H. B. (1991) Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature 350, 614–619.Google Scholar
  41. 41.
    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-DI receptor: selective potentiation by protein kinase A. Mol. Endocrinol 6, 1815–1824.PubMedCrossRefGoogle Scholar
  42. 42.
    Lin, C. W., Miller, T. R., Witter, D. G., Bianchi, B. R., Stashko, M., Manelli, A. M., and Frail, D. E. (1995) Characterization of cloned human dopamine D1 receptor-mediated calcium release in 293 cells. Mol. Pharmacol 47, 131–139.Google Scholar
  43. 43.
    Canonico, P. L., Valdenegro, C. A., and MacLeod, R. M. (1983) The inhibition of phosphatidylinositol turnover: a possible postreceptor mechanism for the prolactin secretion-inhibiting effect of dopamine. Endocrinology 113, 7–14.PubMedCrossRefGoogle Scholar
  44. 44.
    Canonico, P. L. (1989) D-2 dopamine receptor activation reduces free [3H]arachidonate release induced by hypophysiotropic peptides in anterior pituitary cells. Endocrinology 125, 1180–1186.PubMedCrossRefGoogle Scholar
  45. 45.
    Israel, J. M., Kirk, C., and Vincent, J.-D. (1987) Electrophysiological responses to dopamine of rat hypophysial cells in lactotroph-enriched primary cultures. J. Physiol 390, 1–22.PubMedGoogle Scholar
  46. 46.
    Castelletti, L., Memo, M., Missale, C., Spano, P. F., and Valerio, A. (1989) Potassium channels involved in the transduction mechanism of dopamine D2 receptors in rat lactotrophs. J. Physiol 410, 251–265.PubMedGoogle Scholar
  47. 47.
    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
  48. 48.
    Lledo, P. M., Legendre, P., Israel, J. M., and Vincent, J.-D. (1990) Dopamine inhibits two characterized voltage-dependent calcium currents in identified rat lactotroph cells. Endocrinology 127, 990–1001.PubMedCrossRefGoogle Scholar
  49. 49.
    Vallar, L., Vincentini, L. M., and Meldolesi, J. (1988) Inhibition of inositol phosphate production is a late, Ca“-dependent effect of D2 dopaminergic receptor activation in rat lactotroph cells. J. Biol. Chem. 263, 10,127–10, 134.Google Scholar
  50. 50.
    Barber, D. L. (1991) Mechanisms of receptor-mediated regulation of Na-H exchange. Cell. Signalling 3, 387–397.PubMedCrossRefGoogle Scholar
  51. 51.
    Cote., T. E., Grewe, C. W., Tsurata, K., Stoof, J. C., Eskay, R. L., and Kebabian, J. W. (1982) D2 dopamine receptor-mediated inhibition of adenylate cyclase activity in the intermediate lobe of the rat pituitary gland requires guanosine 5’-triphosphate. Endocrinology 110, 812–819.CrossRefGoogle Scholar
  52. 52.
    Williams, P. J., MacVicar, B. A., and Pittman, Q. J. (1989) A dopamine IPSP mediated by an increased potassium conductance. Neuroscience 31, 673–681.PubMedCrossRefGoogle Scholar
  53. 53.
    Williams, P. J., MacVicar, B. A., and Pittman, Q. J. (1990) Synaptic modulation by dopamine of calcium currents in rat pars intermedia. J. Neurosci 10, 757–763.PubMedGoogle Scholar
  54. 54.
    Stack, J. and Surprenant, A. (1991) Dopamine actions on calcium currents, potassium currents and hormone release in rat melanotrophs. J. Physiol 439, 37–58.PubMedGoogle Scholar
  55. 55.
    Keja, J. A., Stoof, J. C., and Kits, K. S. (1992) Dopamine D2 receptor stimulation differentially affects voltage-activated calcium channels in rat pituitary melanotropic cells. J. Physiol 450, 409–435.PubMedGoogle Scholar
  56. 56.
    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. 57.
    Judd, A. M., Login, I. S., Kovacs, K., Ross, P. C., Spangelo, B. L., Jarvis, W. D., and MacLeod, R. M. (1988) Characterization of the MMQ cell, a prolactin-secreting clonal cell line that is responsive to dopamine. Endocrinology 123, 2341–2350.PubMedCrossRefGoogle Scholar
  58. 58.
    Login, I. S., Pancrazio, J. J., and Kim, Y. I. (1990) Dopamine enhances a voltage dependent transient K’ current in the MMQ cell, a clonal pituitary line expressing functional D2 dopamine receptors. Brain Res. 506, 331–334.PubMedCrossRefGoogle Scholar
  59. 59.
    Lledo, P. M., Homburger, V., Bockaert, J., and Vincent, J.-D. (1992) Differential G protein-mediated coupling of D2 receptors to K’ and Ca“ currents in rat anterior pituitary cells. Neuron 8, 455–463.PubMedCrossRefGoogle Scholar
  60. 60.
    Baertschi, A. J., Audigier, Y., Lledo, P.-M., Israel, J.-M., Bockaert, J., and Vincent, J. D. (1992) Dialysis oflactotropes with antisense oligonucleotides assigns guanine nucleotide binding proteins subtypes to their channel effectors. Mol. Endocrinol 6, 2257–2265.Google Scholar
  61. 61.
    Missale, C., Castelletti, L., Boroni, F., Memo, M., and Spano, P. (1991) Epidermal growth factor induces the functional expression of dopamine receptors in the GH3 cell line. Endocrinology 128, 13–20.Google Scholar
  62. 62.
    Gardette, R., Rasolonjanahary, R., Kordon, C., and Enjalbert, A. (1994) Epidermal growth factor treatment induces D2 dopamine receptors functionally coupled to delayed outward potassium current (I K ) in GH4C1 clonal anterior pituitary cells. Neuroendocrinology 59, 10–19.PubMedCrossRefGoogle Scholar
  63. 63.
    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. J. Biol. Chem. 266, 23,392–23, 398.Google Scholar
  64. 64.
    Weiss, S., Sebben, M., Garcia-Sainz, J. A., and Bockaert, J. (1985) D2-dopamine receptor-mediated inhibition of cyclic AMP formation in striatal neurons in primary culture. Mol. Pharmacol 27, 595–599.PubMedGoogle Scholar
  65. 65.
    Freedman, J E and Weight, F. F. (1988) Single K channels activated by D2 receptors in acutely dissociated neurons from rat corpus striatum. Proc. Natl. Acad. Sci. USA 85, 3618–3622.PubMedCrossRefGoogle Scholar
  66. 66.
    Lacey, M. G., Mercuri, N. B., and North, R. A. (1987) Dopamine acts on D2 receptors to increase potassium conductance in neurones of the rat substantia nigra zona compacta. J. Physiol 392, 397–416.PubMedGoogle Scholar
  67. 67.
    Momiyama, T., Todo, N., and Sasa, M. (1993) A mechanism underlying dopamine D1 and D, receptor-mediated inhibition of dopaminergic neurones in the ventral tegmental area in vitro. Br. J. Pharmacol. 109, 933–940.CrossRefGoogle Scholar
  68. 68.
    Roeper, J., Hainsworth, A. H., and Ashcroft, F. M. (1990) Tolbutamide reverses membrane hyperpolarisation induced by activation of D2 receptors and GABAB receptors in isolated substantia nigra neurones. Eur. J. Physiol 416, 473–475.CrossRefGoogle Scholar
  69. 69.
    Lin, Y.-J., Greif, G. J., and Freedman, J. E. (1993) Multiple sulfonylurea-sensitive potassium channels: a novel subtype modulated by dopamine. Mol. Pharmacol 44, 907–910.PubMedGoogle Scholar
  70. 70.
    Freedman, J. E., Greif, G. J., and Lin, Y.-J. (1994) Dual modulation of a K’ channel by dopamine receptors and by cellular metabolism in rat striatum. Neuropsychopharmacology 10, P 124—P 126.Google Scholar
  71. 71.
    Cohen, A. I., Todd, R. D., Harmon, S., and O’Malley, K. L. (1992) Photoreceptors of mouse retinas possess D, receptors coupled to adenylate cyclase. Proc. Natl. Acad. Sci. USA 89, 12,093–12, 097.Google Scholar
  72. 72.
    Albert, P. R., Neve, K. A., Bunzow, J. R., and Civelli, O. (1990) Coupling of a cloned rat dopamine-D2 receptor to inhibition of adenylyl cyclase and prolactin secretion. J. Biol. Chem 265, 2098–2104.PubMedGoogle Scholar
  73. 73.
    Liu, Y. F., Jakobs, K. H., Rasenick, M. M., and Albert, P. R. (1994) G protein specificity in receptor-effector coupling. J. Biol. Chem. 269, 13,880–13, 886.Google Scholar
  74. 74.
    Senogles, S. E. (1994) The D2 dopamine receptor isoforms signal through distinct G,a proteins to inhibit adenylyl cyclase. J. Biol. Chem. 269, 23,120–23, 127.Google Scholar
  75. 75.
    Burris, T. P. and Freeman, M. E. (1994) Comparison of the forms of the dopamine D 2 receptor expressed in GH4CI cells. Proc. Soc. Exptl. Biol. Med 205, 226–235.Google Scholar
  76. 76.
    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
  77. 77.
    Malek, D., Munch, 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
  78. 78.
    McGregor, A. M., Scanlon, M. F., Hall, K., Cook, D., and Hall, R. (1979) Reduction in size of a pituitary tumor by bromocriptine therapy. N Engl. J. Med 300, 291–293.PubMedCrossRefGoogle Scholar
  79. 79.
    Lloyd, H. M., Meares, J. D., and Jacobi, J. (1975) Effects of oestrogen and bromocryptine on in vivo secretion and mitosis in prolactin cells. Nature 255, 497, 498.Google Scholar
  80. 80.
    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
  81. 81.
    Senogles, S. E. (1994) The D2 dopamine receptor mediates inhibition of growth in GH4ZR7 cells: involvement of protein kinase-Ce. Endocrinology 134, 783–789.PubMedCrossRefGoogle Scholar
  82. 82.
    Choi, H. K, Won, L. A., Kontur, P. J., Hammond, D. N., Fox, A. P., Wainer, B. H., Hoffman, P. C., and Heller, A. (1991) Immortalization of embryonic mesencephalic dopaminergic neurons by somatic cell fusion. Brain Res. 552, 67–76.PubMedCrossRefGoogle Scholar
  83. 83.
    Neve, K. A., Henningsen, R. A., Bunzow, J. R., and Civelli, O. (1989) Functional characterization of a rat dopamine D-2 receptor cDNA expressed in a mammalian cell line. Mol. Pharmacol 36, 446–451.Google Scholar
  84. 84.
    Bates, M. D., Senogles, S. E., Bunzow, J. R., Liggett, S. B., Civelli, O., and Caron, M. G. (1991) Regulation of responsiveness at D2 dopamine receptors by receptor desensitization and adenylyl cyclase sensitization. Mol. Pharmacol 39, 55–63.PubMedGoogle Scholar
  85. 85.
    Hayes, G., Biden, T. J., Selbie, L. A., and Shine, J. (1992) Structural subtypes of the dopamine D2 receptor are functionally distinct: expression of the cloned D2A and D2B subtypes in a heterologous cell line. Mol. Endocrinol 6, 920–925.PubMedCrossRefGoogle Scholar
  86. 86.
    Neve, K. A., Kozlowski, M. R., and Rosser, M. P. (1992) Dopamine D2 receptor stimulation of Nam/H’ exchange assessed by quantification of extracellular acidification. J. Biol. Chem. 267, 25,748–25, 753.Google Scholar
  87. 87.
    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
  88. 88.
    Zhang, L.-J., Lachowicz, J. E., and Sibley, D. R. (1994) The D2 and D2L dopamine receptor isoforms are differentially regulated in Chinese hamster ovary cells. Mol. Pharmacol 45, 878–889.PubMedGoogle Scholar
  89. 89.
    Castellano, M. A., Liu, L.-X., Monsma, F. J., Jr., 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 (NG 108–15) cells. Mol. Pharmacol 44, 649–656.PubMedGoogle Scholar
  90. 90.
    Kanterman, R. Y., Mahan, L. C., Briley, E. M., Monsma, F. J., Sibley, D. R., Axelrod, J., and Felder, C. C. (1991) Transfected D2 dopamine receptors mediate the potentiation of arachidonic acid release in Chinese hamster ovary cells. Mol. Pharmacol 39, 364–369.PubMedGoogle Scholar
  91. 91.
    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.Google Scholar
  92. 92.
    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 D1/D2 receptor synergism. Nature 353, 164–167.PubMedCrossRefGoogle Scholar
  93. 93.
    Lahti, R. A., Figur, L. M., Piercey, M. F., Ruppel, P. L., and Evans, D. L. (1992) Intrinsic activity determinations at the dopamine D2 guanine nucleotide-binding protein-coupled receptor: utilization of receptor state binding affinities. Mol. Pharmacol 42, 432–438.PubMedGoogle Scholar
  94. 94.
    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.Google Scholar
  95. 95.
    Lajiness, M. E., Chio, C. L., and Huff, R. M. (1995) Signaling mechanisms of D2, D3, and D4 dopamine receptors determined in transfected cell lines. Clin. Neuropharmacol 18, 525–533.CrossRefGoogle Scholar
  96. 96.
    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.Google Scholar
  97. 97.
    Hescheler, J., Rosenthal, W., Trautwein, W., and Schultz, G. (1987) The GTPbinding protein, Go, regulates neuronal calcium channels. Nature 325, 445–447.PubMedCrossRefGoogle Scholar
  98. 98.
    McFadzean, I Mullaney, I., Brown D. A., and Milligan, G. (1989) Antibodies to the GTP binding protein, Go, antagonize noradrenaline-induced calcium current inhibition in NG108–15 hybrid cells. Neuron 3 177–182.Google Scholar
  99. 99.
    Mullaney, I. and Milligan, G. (1990) Identification of two distinct isoforms ofthe guanine nucleotide binding protein G in neuroblastoma x glioma hybrid cells: independent regulation during cyclic AMP-induced differentiation. J. Neurochem 55, 1890–1898.PubMedCrossRefGoogle Scholar
  100. 100.
    Rouot, B., Charpentier, N., Chabbert, C., Carette, J., Zumbihl, R., Bockaert, J., and Homburger, V. (1992) Specific antibodies against Go isoforms reveal the early expression of the Goa, subunit and appearance of Got,, during neuronal differentiation. Mol. Pharmacol 41, 273–280.PubMedGoogle Scholar
  101. 101.
    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
  102. 102.
    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
  103. 103.
    Todd, R. D., (1992) Neural development is regulated by classical neurotransmitters: dopamine D2 receptor stimulation enhances neurite outgrowth. Biol. Psychiatry 31, 794–807.PubMedCrossRefGoogle Scholar
  104. 104.
    Huff, R. M. and Lajiness, M. E. (1994) D2 dopamine receptors stimulate mitogen activated protein kinases. J. Cell. Biochem 18B, 220.Google Scholar
  105. 105.
    Gupta, S. K., Gallego, C., Johnson, G. L., and Heasley, L. E. (1992) MAP Kinase is constitutively activated in gip2 and src transformed Rat la fibroblasts. J. Biol. Chem 267, 7987–7990.PubMedGoogle Scholar
  106. 106.
    Faure, M., Voyna-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
  107. 107.
    Koch, W. J., Hawes, B. E., Allen, L. F., and Lefkowitz, R J. (1994) Direct evidence that G coupled receptor stimulation of mitogen-activated protein kinase is mediated by Gay activation of p2 Pas. Proc. Natl. Acad. Sci. USA 91 12,706–12,710.Google Scholar
  108. 108.
    Fiore, R. S., Bayer, V. E., Pelech, S. L., Posada, J., Cooper, J. A., and Baraban, J. M. (1993) p42 Mitogen-activated protein kinase in brain: prominent localization in neuronal cell bodies and dendrites. Neuroscience 55, 463–472.Google Scholar
  109. 109.
    Haycock, J. W., Ahn, N. G., Cobb, M. H., and Krebs, E. G. (1992) ERK1 and ERK2, two microtubule-associated protein 2 kinases, mediate the phosphorylation of tyrosine hydroxylase at serine-31 in situ. Proc. Natl. Acad. Sci. USA 89, 2365–2369.CrossRefGoogle Scholar
  110. 110.
    Lin, L.-L., Wartmann, M., Lin, A. Y., Knopf, J. L., Seth, A., and Davis, R. J. (1993) cPLA2 is phosphorylated and activated by MAP kinase. Cell 72, 269–278.Google Scholar
  111. 111.
    Ray, L. B. and Sturgill, T. W. (1987) Rapid stimulation by insulin of a serine/threonine kinase in 3T3–L1 adipocytes that phosphorylates microtubuleassociated protein 2 in vitro. Proc. Natl. Acad. Sci. USA 85, 3753–3757.CrossRefGoogle Scholar
  112. 112.
    Lloyd, E. D. and Wooten, M. W. (1992) PP42144MAP kinase is a component of the neurogenic pathway utilized by nerve growth factor in PC12 cells. J. Neurochem 59, 1099–1109.Google Scholar
  113. 113.
    Freedman, S. B., Patel, S., Marwood, R., Emms, F., Seabrook, G. R., Knowles, M. R., and McAllister, G. (1994) Expression and pharmacological characterization of the human D3 dopamine receptor. J. Pharmacol. Exp. Ther 268, 417–426.PubMedGoogle Scholar
  114. 114.
    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.Google Scholar
  115. 115.
    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
  116. 116.
    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.Google Scholar
  117. 117.
    Cox, B. A., Rosser, M. P., Kozlowski, M. R., Duwe, K. M., Neve, R. L., and Neve, K. A. (1995) Regulation and functional characterization of a rat recombinant dopamine D3 receptor. Synapse 21, 1–9.PubMedCrossRefGoogle Scholar
  118. 118.
    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.Google Scholar
  119. 119.
    Pilon, C., Levesque, 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.Google Scholar
  120. 120.
    Levy, F. O., Zhu, X., Kaumann, A. J., and Birnbaumer, L. (1993) Efficacy of ßi-adrenergic receptors is lower than that of 132-adrenergic receptors. Proc. Natl. Acad. Sci. USA 90, 10,798–10, 802.Google Scholar
  121. 121.
    Van Tol, H. H. M., Bunzow, J. R., Guan, H.-C., Sunahara, R. K., Seeman, P., Niznik, H. B., and Civelli, O. (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 350, 610–614.Google Scholar
  122. 122.
    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 insect cells. FEBS Lett. 320, 130–134.PubMedCrossRefGoogle Scholar
  123. 123.
    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
  124. 124.
    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.PubMedCrossRefGoogle Scholar
  125. 125.
    Van Tol., H. H. M., Wu, C. M., Guan, H.-C., Ohara, K., Bunzow, J. R., Civelli, O., Kennedy, J., Seeman, P., Niznik, H. B., and Jovanovic, V. (1992) Multiple dopamine D4 variants in the human population. Nature 358, 149–152.Google Scholar
  126. 126.
    O’Malley, K. L., Harmon, S., Tang, L., and Todd, R. D. (1992) The rat dopamine D4 receptor: sequence, gene structure, and demonstration of expression in the cardiovascular system. New Biologist 4, 137–146.PubMedGoogle Scholar
  127. 127.
    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, pituitary cells and their regulation by activation of human D2 and D4 dopamine receptors. Br. J. Pharmacol 112, 728–734.PubMedCrossRefGoogle Scholar
  128. 128.
    Kleuss, C., Scherubl, H., Heschler, J., Schultz, G., and Wittig, B. (1992) Different f3-subunits determine G-protein interaction with transmembrane receptors. Nature 358, 424–426.PubMedCrossRefGoogle Scholar
  129. 129.
    Kleuss, C., Scherubl, 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
  130. 130.
    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
  131. 131.
    Di Marzo, 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.PubMedGoogle Scholar
  132. 132.
    Gurwitz, D., Harin, R., Heldman, E., Fraser, C. M., Manor, D., and Fisher, A. (1994) Discrete activation of transduction pathways associated with acetylcholine ml receptor by several muscarinic ligands. Eur. J. Pharmacol 267, 21–31.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Rita M. Huff

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