Mechanisms of Dopaminergic Regulation of Prolactin Secretion

  • Paul R. Albert
  • Mohammad H. Ghahremani
  • Stephen J. Morris
Part of the The Receptors book series (REC)


Dopamine has been recognized as the primary regulator of prolactin (PRL) secretion in vivo for over 20 years (1,2). Hypothalamic dopamine is secreted from tuberoinfundibular neurons at the median eminence of the hypothalamus into the hypophyseal portal blood flow, which directly perfuses the pituitary gland, delivering dopamine at high concentration to anterior pituitary cells. Several lines of evidence suggested that PRL, unlike other pituitary hormones, is under primarily inhibitory hypothalamic regulation, and that dopamine acts as the mediator. Interrupting the portal blood flow to the pituitary by pituitary stalk section results in elevated PRL secretion. The hypersecretion of PRL of the isolated pituitary was reversed by pituitary grafting to an intact portal blood flow (3); by perfusion with hypothalamic extracts containing PIF (PRL inhibitory factor) activity, which was subsequently found to contain dopamine as the active principle (3,4); and by perfusion with dopamine itself (4,5). Dopamine antagonists (e.g., haloperidol) are known to induce hyperprolactinemia and block the PRL-inhibitory actions of dopamine (6,7). Ultimately, dopamine levels measured in portal blood were shown to be sufficient to inhibit PRL secretion in vitro (8),firmly establishing dopamine as the PIF, the only nonpeptide hypothalamic hormone. Thus, tonic inhibition of PRL secretion by dopamine controls the level of PRL in the organism: Decreasing dopamine release leads to enhanced PRL release, mediated in part by stimulatory hormones such as thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP). Enhancement of PRL release correlates with low hypophyseal portal dopamine concentration and is most pronounced during proestrous-estrous, pregnancy, and lactation in the female. The secreted PRL participates in breast and uterine development and milk generation in the breast. In males, PRL levels are low in part because of an absence of circulating estrogen, a powerful inducer of PRL gene transcription (1,2). The present chapter summarizes the current understanding of the mechanisms by which dopamine regulates hormone secretion from the pituitary, focusing primarily on dopaminergic inhibition of PRL secretion.


Potassium Channel Vasoactive Intestinal Peptide Pituitary Cell Prolactin Secretion Anterior Pituitary Cell 
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.
    Ben-Jonathan, N. (1985) Dopamine, a prolactin-inhibiting hormone. Endocrine Rev. 6, 564–589.CrossRefGoogle Scholar
  2. 2.
    Leong, D. A., Frawley, L. S., and Neill, J. D. (1983) Neuroendocrine control of prolactin secretion. Annu. Rev. Physiol. 45, 109–127.PubMedCrossRefGoogle Scholar
  3. 3.
    Lu, K. H. and Meites, J. (1972) Effects of L-dopa on serum prolactin and PIF in intact and hypophysectomized, pituitary-grafted rats. Endocrinology 91, 868–872.Google Scholar
  4. 4.
    Takahara, J., Arimura, A., and Schally, A. V. (1974) Suppression of prolactin release by a purified porcine PIF preparation and catecholamines infused in to a rat hypophysial portal vessel. Endocrinology 95, 462–465.PubMedCrossRefGoogle Scholar
  5. 5.
    Diefenbach, W. P., Carmel, P. W., Frantz, A. G., and Ferin, M. (1976) Suppression of prolactin secretion by L-dopa in the stalk sectioned rhesus monkey. J. Clin. Endocrinol. Metab. 43, 638–642.PubMedCrossRefGoogle Scholar
  6. 6.
    Leblanc, H., Lachelin, G. C. L., Abu-Fadil, S., and Yen, S. S. C. (1976) Effects of dopamine infusion on pituitary secretion in humans. J. Clin. Endocrinol. Metab. 43, 668–674.PubMedCrossRefGoogle Scholar
  7. 7.
    MacLeod, R. M. and Lehmeyer, J. E. (1974) Studies on the mechanism of the dopamine-mediated inhibition ofprolactin secretion. Endocrinology 94, 1077–1085.PubMedCrossRefGoogle Scholar
  8. 8.
    Gibbs, D. M. and Neill, J. D. (1978) Dopamine levels in hypothalmic pituitary stalk blood in the rat are sufficient to inhibit prolactin secretion in vivo. Endocrinology 102, 1895–1900.PubMedCrossRefGoogle Scholar
  9. 9.
    Brown, G. M., Seeman, P., and Lee, T. (1976) Dopamine/neuroleptic receptors in basal hypothalamus and pituitary. Endocrinology 99, 1407–1410.Google Scholar
  10. 10.
    Caron, M. G., Beaulieu, M., Raymond, J., Gagne, B., Drouin, J., Lefkowitz, R. J., and Labrie, F. (1978) Dopaminergic receptor in the anterior pituitary gland: correlation of [3H]dihydroergocryptine binding with the dopaminergic control ofprolactin release. J. Biol. Chem. 253, 2244–2253.PubMedGoogle Scholar
  11. 11.
    DeLean, A., Kilpatrick, B. F., and Caron, M. G. (1982) Dopamine receptor of the porcine anterior pituitary gland: evidence for two affinity states discriminated by both agonists and antagonists. Mol. Pharmacol. 22, 290–297.PubMedGoogle Scholar
  12. 12.
    Birnbaumer, L. (1992) Receptor-to-effector signaling through G proteins: roles for 3y dimers as well as a subunits. Cell 71, 1069–1072.PubMedCrossRefGoogle Scholar
  13. 13.
    Dolphin, A. C. (1987) Nucleotide binding proteins in signal transduction and disease. Trends Neurosci. 10, 53–57.CrossRefGoogle Scholar
  14. 14.
    Cronin, M. J., Myers, G. A., MacLeod, R. M., and Hewlett, E. L. (1983) Pertussis toxin uncouples dopamine agonist inhibition of prolactin release. Am. J. Physiol. 244, E499 — E504.PubMedGoogle Scholar
  15. 15.
    Ohara, K., Haga, K., Berstein, G., Haga, T., Ichiyama, A., and Ohara, K. (1988) The interaction between D-2 dopamine receptors and GTP-binding proteins. Mol. Pharmacol. 33, 290–296.PubMedGoogle Scholar
  16. 16.
    Senogles, S. E., Benovic, J. L., Amlaiky, N., Unson, C., Milligan, G., Vinitsky, R., Spiegel, A., and Caron, M. G. (1987) The D2-dopamine receptor of anterior is functionally associated with a pertussis toxin-sensitive guanine nucleotide binding protein. J. Biol. Chem. 262, 4860–4867.Google Scholar
  17. 17.
    Senogles, S. E., Spiegel, A. M., Padrell, E., Iyengar, R., and Caron, M. G. (1990) Specificity of receptor—G protein interactions. J. Biol. Chem. 265, 4507–4514.PubMedGoogle Scholar
  18. 18.
    Bunzow, J. R., Van Tol, H. H. M., Grandy, D. K., Albert, P., Salon, J., Christie, M., Machida, C. A., Neve, K. A., and Civelli, O. (1988) Cloning and expression of a rat D2 dopamine receptor cDNA. Nature 336, 783–787.PubMedCrossRefGoogle Scholar
  19. 19.
    Civelli, O., Bunzow, J. R., Grandy, D. K., Zhou, Q.-Y., and Van Tol, H. H. M. (1991) Molecular biology of the dopamine receptors. Eur. J. Pharmacol. 207, 277–286.PubMedCrossRefGoogle Scholar
  20. 20.
    Civelli, 0., Bunzow, J. R., and Grandy, D. K. (1993) Molecular diversity of the dopamine receptors. Annu. Rev. Pharmacol. Toxicol. 32, 281–307.Google Scholar
  21. 21.
    Dal Toso, R., Sommer, B., Ewert, M., Herb, A., Pritchett, D. B., Bach, A., Shivers, B. D., and Seeburg, P. H. (1989) The dopamine D2 receptor: two molecular forms generated by alternative splicing. EMBO J 8, 4025–4034.Google Scholar
  22. 22.
    Giros, B., Sokoloff, P., Martres, M.-P., Riou, J.-F., Emorine, L. J., and Schwartz, J. C. (1989) Alternative splicing direct the two D2 dopamine receptor isoforms. Nature 342, 923–926.PubMedCrossRefGoogle Scholar
  23. 23.
    Grandy, D. K., Marchionni, M. A., Makam, H., Stofko, R. E., Alfano, M., Frothingham, L., Fischer, J. B., Burke-Howie, K. J., Bunzow, J. R., Server, A. C., and Civelli, O. (1989) Cloning of the cDNA and gene for a human D2 dopamine receptor. Proc. Natl. Acad. Sci. USA 86, 9762–9766.PubMedCrossRefGoogle Scholar
  24. 24.
    Monsma, F. J., McVittie, L. D., Gerfen, C. R., Mahan, S. C., and Sibley, D. R. (1989) Multiple D2 receptors produced by alternative RNA splicing. Nature 342, 926–929.PubMedCrossRefGoogle Scholar
  25. 25.
    Ostrowski, J., Kjelsberg, M. A., Caron, M. G., and Lefkowitz, R. J. (1992) Mutagenesis ofthe ß2-adrenergic receptor: how structure elucidates function. Annu. Rev. Pharmacol. Toxicol. 32, 167–183.PubMedCrossRefGoogle Scholar
  26. 26.
    Castro, S. W. and Strange, P. G. (1993) Differences in the ligand binding properties of the short and long versions of the D2 dopamine receptor. J. Neurochem. 60, 372–375.PubMedCrossRefGoogle Scholar
  27. 27.
    Malmberg, A., Jackson, D. M., Eriksson, A., and Mohell, N. (1993) Unique binding characteristics of antipsychotic agents interacting with human dopamine D2A, D2B, and D3 receptors. Mol. Pharmacol. 43, 749–754.PubMedGoogle Scholar
  28. 28.
    Porter, T. E., Grandy, D., Bunzow, J., Wiles, C. D., Civelli, 0., and Frawley, L. S. (1994) Evidence that stimulatory dopamine receptors may be involved in the regulation of prolactin secretion. Endocrinology 134, 1263–1268.Google Scholar
  29. 29.
    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-D 1 receptor: selective potentiation by protein kinase A. Mol. Endocrinol. 6, 1815–1824.PubMedCrossRefGoogle Scholar
  30. 30.
    Burris, T. P., Nguyen, D. N., Smith, S. G., and Freeman, M. E. (1992) The stimulatory and inhibitory effects of dopamine on prolactin secretion involved different G-proteins. Endocrinology 130, 926–932.PubMedCrossRefGoogle Scholar
  31. 31.
    Burris, T. P. and Freeman, M. E. (1993) Low concentrations of dopamine increase cytosolic calcium in lactotrophs. Endocrinology 133, 63–68.PubMedCrossRefGoogle Scholar
  32. 32.
    Denef, C., Manet, D., and Dewals, R. (1980) Dopaminergic stimulation of prolactin release. Nature 285, 243–246.PubMedCrossRefGoogle Scholar
  33. 33.
    Gregerson, K. A., Golesorkhi, N., and Chuknyiska, R. (1994) Stimulation of prolactin release by dopamine withdrawal: role of membrane hyperpolarization. Am. J. Physiol. 267, E781 — E788.PubMedGoogle Scholar
  34. 34.
    Gregerson, K. A., Chuknyiska, R., and Golesorkhi, N. (1994) Stimulation of prolactin release by dopamine withdrawal: role of calcium influx. Am. J. Physiol. 267, E789 — E794.PubMedGoogle Scholar
  35. 35.
    Neill, J. D. and Frawley, L. S. (1983) Detection of hormone release from individual cells in mixed populations using a reverse hemolytic plaque assay. Endocrinology 112, 1135–1137.Google Scholar
  36. 36.
    Tashjian, A. H., Jr. (1979) Clonal strains of hormone-producing pituitary cells. Methods Enzymol. 58, 527–535.PubMedCrossRefGoogle Scholar
  37. 37.
    Tashjian, A. H., Jr., Yasumura, Y., Levine, L., Sato, G. H., and Parker, M. L. (1968) Establishment of clonal strains of rat pituitary tumor cells that secrete growth hormone. Endocrinology 82, 342–352.PubMedCrossRefGoogle Scholar
  38. 38.
    Frawley, L. S. and Boockfor, F. R. (1991) Mammosomatotropes: presence and functions in normal and neoplastic pituitary tissue. Endo. Rev. 12, 337–355.CrossRefGoogle Scholar
  39. 39.
    Porter, T., Hill, J. B., Wiles, C. D., and Stephen, L. (1990) Is the mammosomatotroph a transitional cell for the functional interconversion of growth hormone-and prolactin-secreting cells? Suggestive evidence from virgin, gestating, and lactating rats. Endocrinology 127, 2789–2794.PubMedCrossRefGoogle Scholar
  40. 40.
    Albert, P. R. (1994) Heterologous expression of G protein-coupled receptors in pituitary and fibroblast cell lines. Vitamins Hormones 48, 59–109.PubMedCrossRefGoogle Scholar
  41. 41.
    Albert, P. R., Neve, K., Bunzow, J., and Civelli, O. (1990) Coupling of a rat dopamine D2 receptor to inhibition of adenylyl cyclase and prolactin secretion. J. Biol. Chem. 265, 2098–2104.Google Scholar
  42. 42.
    Cronin, M. J., Faure, N., Martial, J. A., and Weiner, R. I. (1980) Absence of high affinity dopamine receptor in GH3 cells: a prolactin secreting clone resistant to the inhibitory action of dopamine. Endocrinology 106, 718–723.Google Scholar
  43. 43.
    Missale, C., Boroni, F., Sigala, S., Castelletti, L., Falardeau, P., Dal Toso, R., Balsari, A., and Spano, P. (1994) Epidermal growth factor promotes uncoupling from adenylyl cyclase of the rat D2S receptor expressed in GH4C 1 cells. J. Neurochem. 62, 907–915.Google Scholar
  44. 44.
    Missale, C., Boroni, F., Castelletti, L., Dal Toso, R., Gabellini, N., Sigala, S., and Spano, P. (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
  45. 45.
    Missale, C., Boroni, F., Sigala, S., Zanellato, A., Dal Toso, R., Balsari, A., and Spano, P. (1994) Nerve growth factor directs differentiation of the bipotential cell line GH-3 into the mammotroph phenotype. Endocrinology 136, 290–298.CrossRefGoogle Scholar
  46. 46.
    Enjalbert, A. and Bockaert J. (1983) Pharmacological characterization of the D2 dopamine receptor negatively coupled with adenylate cyclase in rat anterior pituitary. Mol. Pharmacol. 23, 576–584.PubMedGoogle Scholar
  47. 47.
    De Camilli, P., Macconi, D., and Spada, A. (1979) Dopamine inhibits adenylate cyclase in human prolactin-secreting pituitary tumors. Nature 278, 252–254.PubMedCrossRefGoogle Scholar
  48. 48.
    Biales, M., Dichter, M. A., and Tischler, A. (1977) Sodium and calcium action potential in pituitary cells. Nature 267, 172–174.PubMedCrossRefGoogle Scholar
  49. 49.
    Kidokoro, Y. (1975) Spontaneous calcium action potentials in a clonal pituitary cell line and their relationship to prolactin secretion. Nature 258, 741, 742.Google Scholar
  50. 50.
    Schlegel, W., Winiger, B. P., Mollard, P., Vacher, P., Wuarin, F., Zahnd, G. R., Wollheim, C. B., and Dufy, B. (1987) Oscillations of cytosolic Cat’ in pituitary cells due to action potentials. Nature 329, 719–721.PubMedCrossRefGoogle Scholar
  51. 51.
    Taraskevich, P. S. and Douglas, W. W. (1977) Action potentials occur in cells of the normal anterior pituitary gland and are stimulated by the hypophysiotropic peptide thyrotropin-releasing hormone. Proc. Natl. Acad. Sci. USA 74, 4064–4067.PubMedCrossRefGoogle Scholar
  52. 52.
    Taraskevich, P. S. and Douglas, W. W. (1978) Catecholamines of supposed inhibitory hypophysiotropic function suppress action potentials in prolactin cells. Nature 276, 832–834.PubMedCrossRefGoogle Scholar
  53. 53.
    Taraskevich, P. S. and Douglas, W. W. (1980) Electrical behaviour in a line of anterior pituitary cells (GH cells) and the influence of the hypothalamic peptide, thyrotropin releasing factor. Neuroscience 5, 421–431.PubMedCrossRefGoogle Scholar
  54. 54.
    Burris, T. P. and Freeman, M. E. (1994) Comparison of the forms of the dopamine D2 receptor expressed in GH4C1 cells. Proc. Soc. Exp. Med. Biol. 205, 226–235.Google Scholar
  55. 55.
    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.CrossRefGoogle Scholar
  56. 56.
    Vallar, L., Claudia, M., Magni, M., Albert, P., Bunzow, J., Meldolesi, J., and Civelli, O. (1990) Differential coupling of dopaminergic D2 receptor expressed in different cell types. J. Biol. Chem. 265, 10,320–10, 326.Google Scholar
  57. 57.
    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 Gi2 in GH4C1 pituitary cells. J. Biol. Chem. 269, 13,880–13, 886.Google Scholar
  58. 58.
    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
  59. 59.
    Seabrook, G. R., Knowles, M., Brown, N., Myers, J., Sinclair, H., Patel, S., Freedman, S. B., and McAllister (1994) Pharmacology of high-threshold calcium currents in GH4C1 pituitary cells and their regulation by activation of human D2 and D4 receptors. Br. J. Pharmacol. 112, 728–734.PubMedCrossRefGoogle Scholar
  60. 60.
    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. 61.
    Einhorn, L. C. and Oxford, G. S. (1993) Guanine nucleotide binding proteins mediate D2 dopamine receptor activation of a potassium channel in rat lactotrophs. J. Physiol. 462, 563–578.PubMedGoogle Scholar
  62. 62.
    Florio, T., Pan, M., 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
  63. 63.
    Senogles, S. E. (1994) The D2 dopamine receptor mediates inhibition of growth in GH4ZR7 cells: involvement of protein kinase-Cs. Endocrinology 134, 783–789.PubMedCrossRefGoogle Scholar
  64. 64.
    Nilsson, C. and Eriksson, E. (1992) Partial dopamine D2 receptor agonists antagonize prolactin-regulating D2 receptors in a transfected clonal cell line (GH4ZR7). Eur. J. Pharmacol. 218, 205–211.PubMedCrossRefGoogle Scholar
  65. 65.
    Elsholtz, H. P., Lew, A. M., Albert, P. R., and Sundmark, V. C. (1991) Inhibitory control of prolactin and Pit-1 gene promoters by dopamine. Dual signaling pathways required for D2 receptor-regulated expression of the prolactin gene. J. Biol. Chem. 266, 22,919–22, 925.Google Scholar
  66. 66.
    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
  67. 67.
    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, 920–926.PubMedCrossRefGoogle Scholar
  68. 68.
    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
  69. 69.
    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
  70. 70.
    Di Marzo, V., Vial, D., Sokoloff, P., Schwartz, J.-C., and Piomelli, D. (1993) Selection of alternative Gi-mediated signaling pathways at the dopamine D2 receptor by protein kinase C. J. Neurosci. 13, 4846–4853.PubMedGoogle Scholar
  71. 71.
    Kanterman, R. Y., Mahan, L. C., Briley, E. M., Monsma, F. J., Jr., Sibley, D. R., Axelrod, J., and Felder, C. C. (1990) Transfected D2 dopamine receptors mediate the potentiation of arachidonic acid release in Chinese hamster ovary cells. Mol. Pharmacol. 39, 364–369.Google Scholar
  72. 72.
    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
  73. 73.
    Clapham, D. E. and Neer, E. J. (1993) New roles for G-protein ßy-dimers in trans-membrane signalling. Nature 365, 403–406.Google Scholar
  74. 74.
    Albert, P. R. and Morris, S. J. (1994) Antisense knockouts: molecular scalpels for the dissection of signal transduction. Trends Pharmacol. Sci. 15, 250–254.Google Scholar
  75. 75.
    Lledo, P.-M., Homburger, V., Bockeart, 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
  76. 76.
    Kleuss, C., Hescheler, J., Ewel, C., Rosenthal, W., Schultz, G., and Wittig, B. (1991) Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents. Nature 353, 43–48.PubMedCrossRefGoogle Scholar
  77. 77.
    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.Google Scholar
  78. 78.
    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
  79. 79.
    Yatani, A., Codina, J., Sekura, R. D., Birnbaumer, L., and Brown, A. M. (1987) Reconstitution of somatostatin and muscarinic receptor mediated stimulation of K’ channels by isolated GK protein in clonal rat anterior pituitary membranes. Mol. Endocrinol. 1, 283–289.PubMedCrossRefGoogle Scholar
  80. 80.
    Yatani, A., Mattera, R., Codina, J., Graf, R., Okabe, K., Padrell, E., Iyengar, R., Brown, A. M., and Birnbaumer, L. (1988) The G protein-gated atrial K’ channel is stimulated by three distinct Ga subunits. Nature 336, 680–682.PubMedCrossRefGoogle Scholar
  81. 81.
    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 protein subtypes to their channel effectors. Mol. Endocrinol. 6, 2257–2265.PubMedCrossRefGoogle Scholar
  82. 82.
    White, R. E., Schonbrunn, A., and Armstrong, D. L. (1991) Somatostatin stimulates Ca’-activated K’ channels through protein dephosphorylation. Nature 351, 570–573.PubMedCrossRefGoogle Scholar
  83. 83.
    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
  84. 84.
    Dorflinger, L. J. and Schonbrunn, A. (1983) Somatostatin inhibits vasoactive intestinal peptide-stimulated cyclic adenosine monophosphate accumulation in GH pituitary cells. Endocrinology 113, 1541–1550.PubMedCrossRefGoogle Scholar
  85. 85.
    Dorflinger, L. J. and Schonbrunn, A. (1983) Somatostatin inhibits basal and vasoactive intestinal peptide-stimulated hormone release by different mechanisms in GH pituitary cells. Endocrinology 113, 1551–1560.PubMedCrossRefGoogle Scholar
  86. 86.
    Gourdji, D., Bataille, D., Vauclin, N., Grouselle, D., Rosselin, G., and TixierVidal, A. (1979) Vasoactive intestinal peptide (VIP) stimulates prolactin (PRL) release and cAMP production in a rat pituitary cell line (GH3/B6). Additive effects of VIP and TRH on PRL release. FEBS Lett. 104, 165–168.Google Scholar
  87. 87.
    Guild, S. and Drummond, A. H. (1984) Vasoactive-intestinal-polypeptide-stimulated adenosine 3’,5’-cyclic monophosphate accumulation in GH3 pituitary tumour cells. Biochem. J. 221, 789–796.PubMedGoogle Scholar
  88. 88.
    Cooper, D. M. F., Bier-Laning, C. M., Halford, M. K., Ahlijannian, M. K., and Zahniser, N. R. (1986) Dopamine, acting through D2 receptors, inhibits rat striatal adenylate cyclase by a GTP-dependent process. Mol. Pharmacol. 29, 113–119.PubMedGoogle Scholar
  89. 89.
    Bates, M. D., Senogles, S. E., Bunzow, J. R., Liggett, S. B., Civelli, O., and Caron, M. G. (1990) Regulation of responsiveness at D2 dopamine receptors by receptor desensitization and adenylyl cyclase sensitization. Mol. Pharmacol. 39, 55–63.Google Scholar
  90. 90.
    Delbeke, D., Scammell, J. G., Martinez-Campos, A., and Dannies, P. S. (1986) Dopamine inhibits prolactin release when cyclic adenosine 3’5’-cyclic monophosphate levels are elevated. Endocrinology 118, 1271–1277.Google Scholar
  91. 91.
    Koch, B. D., Dorflinger, L. J., and Schonbrunn, A. (1985) Pertussis toxin blocks both cyclic AMP-mediated and cyclic AMP-independent actions of somatostatin. Evidence for coupling of Ni to decreases in intracellular free calcium. J. Biol. Chem. 260, 13,138–13, 145.Google Scholar
  92. 92.
    Koch, B. D., Blalock, J. B., and Schonbrunn, A. (1988) Characterization of the cyclic AMP-independent actions of somatostatin in GH cells. I. An increase in potassium conductance is responsible for both the hyperpolarization and the decrease in intracellular free calcium produced by somatostatin. J. Biol. Chem. 263, 216–225.PubMedGoogle Scholar
  93. 93.
    Koch, B. D. and Schonbrunn, A. (1988) Characterization of the cyclic AMP-independent actions of somatostatin in GH cells. II. An increase in potassium conductance initiates somatostatin-induced inhibition ofprolactin secretion. J. Biol. Chem. 263, 226–234.PubMedGoogle Scholar
  94. 94.
    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 (IK) in GH4C1 clonal anterior pituitary cells. Neuroendocrinology 59, 10–19.PubMedCrossRefGoogle Scholar
  95. 95.
    Memo, M., Castelletti, L., Missale, C., Valerio, A., Carruba, M., and Spano, P. (1986) Dopaminergic inhibition ofprolactin release and calcium influx induced by neurotensin in anterior pituitary is independent of cyclic AMP system. J. Neurochem. 47, 1689–1695.PubMedCrossRefGoogle Scholar
  96. 96.
    Cohen, C. J. and McCarthy, R. T. (1987) Nimodipine block of calcium channels in rat anterior pituitary cells. J. Physiol. 387, 195–225.PubMedGoogle Scholar
  97. 97.
    Albert, P. R. and Tashjian, A. H., Jr. (1984) Thyrotropin-releasing hormone-induced spike and plateau in cytosolic free Ca“ concentrations in pituitary cells: relation to prolactin release. J. Biol. Chem. 259, 5827–5832.PubMedGoogle Scholar
  98. 98.
    Albert, P. R. and Tashjian, A. H., Jr. (1984) Relationship of thyrotropin-releasing hormone-induced spike and plateau phases in cytosolic free Ca“ concentrations to hormone secretion: selective blockade using ionomycin and nifedipine. J. Biol. Chem. 259, 15,350–15, 363.Google Scholar
  99. 99.
    Aragay, A. M., Katz, A., and Simon, M. I. (1992) The Gaq and Gai proteins couple the thyrotropin-releasing hormone receptor to phospholipase C in GH3 rat pituitary cells. J. Biol. Chem. 267, 24,983–24,988.Google Scholar
  100. 100.
    Berridge, M. J. (1993) Inositol trisphosphate and calcium signalling. Nature 361, 315–325.PubMedCrossRefGoogle Scholar
  101. 101.
    Nishizuka, Y. (1988) The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 334, 661–665.PubMedCrossRefGoogle Scholar
  102. 102.
    Aizawa, T. and Hinkle, P. M. (1985) Thyrotropin-releasing hormone rapidly stimulates a biphasic secretion of prolactin and growth hormone in GH4C 1 rat pituitary tumor cells. Endocrinology 116, 73–82.PubMedCrossRefGoogle Scholar
  103. 103.
    Albert, P. R. and Tashjian, A. H., Jr. (1985) Dual actions of phorbol esters on cytosolic free Ca`* concentrations and reconstitution with ionomycin of acute thyrotropin-releasing hormone responses. J. Biol. Chem. 260, 8746–8759.PubMedGoogle Scholar
  104. 104.
    Albert, P. R. and Tashjian, A. H., Jr. (1986) lonomycin acts as an ionophore to release TRH-regulated Ca“ stores from GH4C1 cells. Am. J. Physiol. 251, C887—C891.Google Scholar
  105. 105.
    Albert, P. R., Wolfson, G., and Tashjian, A. H., Jr. (1987) Diacylglycerol increases cytosolic free Ca“ concentration in rat pituitary cells. Relationship to thyrotropinreleasing hormone action. J. Biol. Chem. 262, 6577–6581.Google Scholar
  106. 106.
    Dubinski, J. M. and Oxford, G. S. (1985) Dual modulation of K channels by thyrotropin-releasing hormone in clonal pituitary cells. Proc. Natl. Acad. Sci. USA 82, 4282–4286.CrossRefGoogle Scholar
  107. 107.
    Gollasch, M., Kleuss, C., Hescheler, J., Wittig, B., and Schulz, G. (1993) Gi2 and protein kinase C are required for thyrotropin-releasing hormone-induced stimulation of voltage-dependent Cat+ channels in rat pituitary GH3 cells. Proc. Natl. Acad. Sci. USA 90, 6265–6269.PubMedCrossRefGoogle Scholar
  108. 108.
    Law, G. J., Pachter, J. A., and Dannies, P. S. (1988) Dopamine has no effect on thyrotropin-releasing hormone mobilization of calcium from intracellular stores in rat anterior pituitary cells. Mol. Endocrinol. 2, 966–972.PubMedCrossRefGoogle Scholar
  109. 109.
    Malgaroli, A., Vallar, L., Elahi, F. R., Pozzan, T., Spada, A., and Meldolesi, J. (1987) Dopamine inhibits cytosolic Caz+ increases in rat lactotroph cells. J. Biol. Chem. 262, 13,920–13, 927.Google Scholar
  110. 110.
    Vallar, L., Vicentini, L. M., and Meldolesi, J. M. (1988) Inhibition of inositol phosphate production is a late, Caz+-dependent effect of D2 dopaminergic receptor activation in rat lactotroph cells. J. Biol. Chem. 263, 10,127–10, 134.Google Scholar
  111. 111.
    Vallar, L. and Meldelosi, J. (1989) Mechanisms of signal transduction at the dopamine D2 receptor. Trends Pharmacol. Sci. 10, 74–77.PubMedCrossRefGoogle Scholar
  112. 112.
    Kineman, R. D., Gettys, T. W., and Frawley, L. S. (1994) Paradoxical effects of dopamine (DA): Gia3 mediates DA inhibition of PRL release while masking its PRL-releasing activity. Endocrinology 135, 790–793.PubMedCrossRefGoogle Scholar
  113. 113.
    Albert, P. R. and Raquidan, D. (1995) Dopamine-D2 receptor routing through multiple G proteins for inhibition of TRH-stimulated prolactin secretion. Proc. Endocrine Soc. 77, 113.Google Scholar
  114. 114.
    Armstrong, C. M. and Matteson, D. R. (1985) Two distinct populations of calcium channels in a clonal line of pituitary cells. Science 227, 65–67.PubMedCrossRefGoogle Scholar
  115. 115.
    Enjalbert, A., Musset, F., Chenard, C., Priam, M., Kordon, C., and Heisler, S. (1988) Dopamine inhibits prolactin secretion stimulated by the calcium channel agonist Bay-K-8644 through a pertussis toxin-sensitive G protein in anterior pituitary cells. Endocrinology 123, 406–412.PubMedCrossRefGoogle Scholar
  116. 116.
    Rendt, J. and Oxford, G. S. (1994) Absence of coupling between D2 dopamine receptors and calcium channels in lactotrophs from cycling female rats. Endocrinology 135, 501–508.PubMedCrossRefGoogle Scholar
  117. 117.
    Denef, C., Baes, M., and Schramme, C. (1984) Stimulation of prolactin secretion after short term or pulsatile exposure to dopamine in superfused anterior pituitary cell aggregates. Endocrinology 114, 1371–1378.PubMedCrossRefGoogle Scholar
  118. 118.
    Chen, C., Zheng, J., Israel, J. M., Clarke, I. J., and Vincent, J. D. (1993) Mechanism of the prolactin rebound after withdrawal in rat pituitary cells. Am. J. Physiol. 265, E 145—E 152.Google Scholar
  119. 119.
    Van den Berghe, G., De Zegher, F., and Lauwers, P. (1994) Dopamine suppresses pituitary function in infants and children. Crit. Care Med. 22, 1747–1753.Google Scholar
  120. 120.
    Lledo, P.-M., Vernier, P., Vincent, J.-D., Mason, W. T., and Zorec, R. (1993) Inhibition of Rab3B expression attenuates Caz+-dependent exocytosis in rat anterior pituitary cells. Nature 364, 540–543.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Paul R. Albert
  • Mohammad H. Ghahremani
  • Stephen J. Morris

There are no affiliations available

Personalised recommendations