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Targeting the ghrelin receptor

Orally active GHS and cortistatin analogs

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Abstract

Ghrelin has been discovered as a natural ligand of the receptor specific for synthetic GH secretagogues (GHS). Ghrelin as well as synthetic GHS not only possess a remarkable GH-releasing activity but are also endowed with other endocrine and nonendocrine activities including orexigenic action, influence on gastro-enteropancreatic functions, and cardiovascular and anti-proliferative effects. Based on these data, particular effort has been focused on the isolation of new putative natural ligands of the GHS-receptors (GHS-R) and on the identification of synthetic compounds endowed with agonistic or antagonistic activity. For instance, ghrelin analogs acting as agonists or antagonists would be able to enhance or reduce appetite and food intake; these molecules would receive obvious interest for treatment of eating disorders and obesity, respectively. Ghrelin and its orally active, agonistic analogs could have prespectives for diagnosis and treatment of GH insufficiency. In this context, EP1572, a selective, orally active, peptidomimetic GHS as well as cortistatin, another putative, natural ligand of the GHS-R, and its analogs, are currently under investigation.

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References

  1. Smith, R. G., Van der Ploeg, L. H., Howard, A. D., et al. (1997). Endocr. Rev. 18, 621–645.

    Article  PubMed  CAS  Google Scholar 

  2. Bowers, C. Y. (1998). Cell. Mol. Life Sci. 54, 1316–1329.

    Article  PubMed  CAS  Google Scholar 

  3. Ghigo, E., Arvat, E., Giordano, R., et al. (2001). Endocrine 14, 87–93.

    Article  PubMed  CAS  Google Scholar 

  4. Chapman, I. M., Bach, M. A., Van Cauter, E., et al. (1996). J. Clin. Endocrinol. Metab. 81, 4249–4257.

    Article  PubMed  CAS  Google Scholar 

  5. Ghigo, E., Arvat, E., Aimaretti, G., Broglio, F., Giordano, R., and Camanni, F. (1998). In: Baillieres clinical endocrinology and metabolism. Shalet, S. M. (eds.). Bailliere Tindall: London.

    Google Scholar 

  6. Ghigo, E., Arvat, E., and Camanni, F. (1998). Ann. Med. 30, 159–168.

    PubMed  CAS  Google Scholar 

  7. Howard, A. D., Feighner, S. D., Cully, D. F., et al. (1996). Science 273, 974–977.

    Article  PubMed  CAS  Google Scholar 

  8. Smith, R. G., Leonard, R., Bailey, A. R., et al. (2001). Endocrine 14, 9–14.

    Article  PubMed  CAS  Google Scholar 

  9. Smith, R. G., Palyha, O. C., Feighner, S. D., et al. (1999). Horm. Res. 51, 1–8.

    PubMed  CAS  Google Scholar 

  10. Papotti, M., Ghe, C., Cassoni, P., et al. (2000). J. Clin. Endocrinol. Metab. 85, 3803–3807.

    Article  PubMed  CAS  Google Scholar 

  11. Gnanapavan, S., Kola, B., Bustin, S. A., et al. (2002). J. Clin. Endocrinol. Metab. 87, 2988–2992.

    Article  PubMed  CAS  Google Scholar 

  12. Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., and Kangawa, K. (1999). Nature 402, 656–660.

    Article  PubMed  CAS  Google Scholar 

  13. Date, Y., Kojima, M., Hosoda, H., et al. (2000). Endocrinology 141, 4255–4261.

    Article  PubMed  CAS  Google Scholar 

  14. Mori, K., Yoshimoto, A., Takaya, K., et al. (2000). FEBS Lett. 486, 213–216.

    Article  PubMed  CAS  Google Scholar 

  15. Gualillo, O., Caminos, J., Blanco, M., et al. (2001). Endocrinology 142, 788–794.

    Article  PubMed  CAS  Google Scholar 

  16. Kanamoto, N., Akamizu, T., Hosoda, H., et al. (2001). J. Clin. Endocrinol. Metab. 86, 4984–4890.

    Article  PubMed  CAS  Google Scholar 

  17. Kojima, M., Hosoda, H., and Kangawa, K. (2001). Horm. Res. 56, 93–97.

    Article  PubMed  CAS  Google Scholar 

  18. Korbonits, M., Bustin, S. A., Kojima, M., et al. (2001). J. Clin. Endocrinol. Metab. 86, 881–887.

    Article  PubMed  CAS  Google Scholar 

  19. Date, Y., Nakazato, M., Hashiguchi, S., et al. (2002). Diabetes 51, 124–129.

    Article  PubMed  CAS  Google Scholar 

  20. Tena-Sempere, M., Barreiro, M. L., Gonzalez, L. C., et al. (2002). Endocrinology 143, 717–725.

    Article  PubMed  CAS  Google Scholar 

  21. Volante, M., Allia, E., Gugliotta, P., et al. (2002). J. Clin. Endocrinol. Metab. 87, 1300–1308.

    Article  PubMed  CAS  Google Scholar 

  22. Bednarek, M. A., Feighner, S. D., Pong, S. S., et al. (2000). J. Med. Chem. 43, 4370–4376.

    Article  PubMed  CAS  Google Scholar 

  23. Matsumoto, M., Hosoda, H., Kitajima, Y., et al. (2001). Biochem. Biophys. Res. Commun. 287, 142–146.

    Article  PubMed  CAS  Google Scholar 

  24. Muccioli, G., Papotti, M., Locatelli, V., Ghigo, E., and Deghenghi, R. (2001). J. Endocrinol. Invest. 24, RC7-RC9.

    PubMed  CAS  Google Scholar 

  25. Hosoda, H., Kojima, M., Matsuo, H., and Kangawa, K. (2000). Biochem. Biophys. Res. Commun. 279, 909–913.

    Article  PubMed  CAS  Google Scholar 

  26. Broglio, F., Benso, A., Gottero, C., et al. (2003). J. Endocrinol. Invest. 26, 192–196.

    PubMed  CAS  Google Scholar 

  27. Smith, R. G., Griffin, P. R., Xu, Y., et al. (2000). Biochem. Biophys. Res. Commun. 276, 1306–1313.

    Article  PubMed  CAS  Google Scholar 

  28. Tullin, S., Hansen, B. S., Ankersen, M., Moller, J., Von Cappelen, K. A., and Thim, L. (2000). Endocrinology 141, 3397–3402.

    Article  PubMed  CAS  Google Scholar 

  29. Chen, C. (2000). Clin. Exp. Pharmacol. Physiol. 27, 323–329.

    Article  PubMed  CAS  Google Scholar 

  30. Torsello, A., Locatelli, V., Melis, M. R., et al. (2000). Neuroendocrinology 72, 327–332.

    Article  PubMed  CAS  Google Scholar 

  31. Muccioli, G., Tschop, M., Papotti, M., Deghenghi, R., Heiman, M., and Ghigo, E. (2002). Eur. J. Pharmacol. 440, 235–254.

    Article  PubMed  CAS  Google Scholar 

  32. Baldanzi, G., Filigheddu, N., Cutrupi, S., et al. (2002). J. Cell Biol. 159, 1029–1037.

    Article  PubMed  CAS  Google Scholar 

  33. Bedendi, I., Alloatti, G., Marcantoni, A., et al. (2003). Eur. J. Pharmacol. (in press).

  34. Cassoni, P., Papotti, M., Ghe, C., et al. (2001). J. Clin. Endocrinol. Metab. 86, 1738–1745.

    Article  PubMed  CAS  Google Scholar 

  35. Muccioli, G., Ghe, C., Ghigo, M. C., et al. (1998). J. Endocrinol. 157, 99–106.

    Article  PubMed  CAS  Google Scholar 

  36. Ong, H., Bodart, V., McNicoll, N., Lamontagne, D., and Bouchard, J. F. (1998). Growth Horm. IGF Res. 8, 137–140.

    Article  PubMed  CAS  Google Scholar 

  37. Bodart, V., Bouchard, J. F., McNicoll, N., et al. (1999). Circul. Res. 85, 796–802.

    CAS  Google Scholar 

  38. Toth, K., Kovacs, M., Zarandi, M., et al. (1998). J. Pept. Res. 51, 134–141.

    Article  PubMed  CAS  Google Scholar 

  39. Melis, M. R., Succu, S., Spano, M. S., et al. (2001). Eur. J. Pharmacol. 411, 305–310.

    Article  PubMed  CAS  Google Scholar 

  40. Deghenghi, R., Papotti, M., Ghigo, E., and Muccioli, G. (2001). J. Endocrinol. Invest. 24, RC1-RC3.

    PubMed  CAS  Google Scholar 

  41. Deghenghi, R., Papotti, M., Ghigo, E., Muccioli, G., and Locatelli, V. (2001). Endocrine 14, 29–33.

    Article  PubMed  CAS  Google Scholar 

  42. Yoshihara, F., Kojima, M., Hosoda, H., Nakazato, M., and Kangawa, K. (2002). Curr. Opin. Clin. Nutr. Metab. Care 5, 391–395.

    Article  PubMed  CAS  Google Scholar 

  43. Ukkola, O. (2003). Eur. J. Clin. Invest. 33, 183–185.

    Article  PubMed  CAS  Google Scholar 

  44. Tannenbaum, G. S., Epelbaum, J., and Bowers, C. Y. (2003). Endocrinology 144, 967–974.

    Article  PubMed  CAS  Google Scholar 

  45. Kamegai, J., Tamura, H., Shimizu, T., Ishii, S., Sugihara, H., and Wakabayashi, I. (2000). Endocrinology 141, 4797–4800.

    Article  PubMed  CAS  Google Scholar 

  46. Tannenbaum, G. S. and Bowers, C. Y. (2001). Endocrine 14, 21–27.

    Article  PubMed  CAS  Google Scholar 

  47. Wren, A. M., Small, C. J., Fribbens, C. V., et al. (2002). Neuroendocrinology 76, 316–324.

    Article  PubMed  CAS  Google Scholar 

  48. Broglio, F., Benso, A., Gottero, C., et al. (2002). Clin. Endocrinol. 57, 265–271.

    Article  CAS  Google Scholar 

  49. Di Vito, L., Broglio, F., Benso, A., et al. (2002). Clin. Endocrinol. 56, 643–648.

    Article  Google Scholar 

  50. Arvat, E., Giordano, R., Broglio, F., et al. (2000). J. Anti-Aging Med. 3, 149–158.

    Article  CAS  Google Scholar 

  51. Gottero, C., Benso, A., Prodam, F., et al. (2002). J. Endocrinol. Invest. 25, 42–43.

    PubMed  CAS  Google Scholar 

  52. Broglio, F., Benso, A., Castiglioni, C., et al. (2003). J. Clin. Endocrinol. Metab. 88, 1537–1542.

    Article  PubMed  CAS  Google Scholar 

  53. Leal-Cerro, A., Garcia, E., Astorga, R., Casanueva, F. F., and Dieguez, C. (1995). Eur. J. Endocrinol. 132, 712–715.

    Article  PubMed  CAS  Google Scholar 

  54. Popovic, V., Leal, A., Micic, D., et al. (2000). Lancet 356, 1137–1142.

    Article  PubMed  CAS  Google Scholar 

  55. Yu, H., Cassorla, A., Tiulpakov, A., et al. (1998). In: The Endocrine Society 80th Annual Meeting.

  56. Copinschi, G., Leproult, R., Van Onderbergen, A., et al. (1997). Neuroendocrinology 66, 278–286.

    PubMed  CAS  Google Scholar 

  57. Van Cauter, E., Plat, L., and Copinschi, G. (1998). Sleep 21, 553–566.

    PubMed  Google Scholar 

  58. Murphy, M. G., Plunkett, L. M., Gertz, B. J., et al. (1998). J. Clin. Endocrinol. Metab. 83, 320–325.

    Article  PubMed  CAS  Google Scholar 

  59. Svensson, J., Lonn, L., Jansson, J. O., et al. (1998). J. Clin. Endocrinol. Metab. 83, 362–369.

    Article  PubMed  CAS  Google Scholar 

  60. Murphy, M. G., Weiss, S., McClung, M., et al. (2001). J. Clin. Endocrinol. Metab. 86, 1116–1125.

    Article  PubMed  CAS  Google Scholar 

  61. Broglio, F., Gottero, C., Benso, A., et al. (2003). Endocrine 22, 19–24.

    Article  PubMed  CAS  Google Scholar 

  62. Broglio, F., Arvat, E., Benso, A., et al. (2001). J. Clin. Endocrinol. Metab. 86, 5083–5086.

    Article  PubMed  CAS  Google Scholar 

  63. Arosio, M., Ronchi, C. L., Gebbia, C., Cappiello, V., Beck-Peccoz, P., and Peracchi, M. (2003). J. Clin. Endocrinol. Metab. 88, 701–704.

    Article  PubMed  CAS  Google Scholar 

  64. Shuto, Y., Shibasaki, T., Otagiri, A., et al. (2001). J. Clin. Invest. 109, 1429–1436.

    Article  CAS  Google Scholar 

  65. Nakazato, M., Murakami, N., Date, Y., et al. (2001). Nature 409, 194–198.

    Article  PubMed  CAS  Google Scholar 

  66. Tschop, M., Smiley, D. L., and Heiman, M. L. (2000). Nature 407, 908–913.

    Article  PubMed  CAS  Google Scholar 

  67. Cowley, M. A., Smith, R. G., Diano, S., et al. (2003). Neuron 37, 649–661.

    Article  PubMed  CAS  Google Scholar 

  68. Lawrence, C. B., Snape, A. C., Baudoin, F. M., and Luckman, S. M. (2002). Endocrinology 143, 155–162.

    Article  PubMed  CAS  Google Scholar 

  69. Kalra, S. P., Bagnasco, M., Otukonyong, E. E., Dube, M. G., and Kalra, P. S. (2003). Regul. Pept. 111, 1–11.

    Article  PubMed  CAS  Google Scholar 

  70. Small, C. J., Stanley, S. A., and Bloom, S. R. (2002). Semin. Reprod. Med. 20, 389–398.

    Article  PubMed  CAS  Google Scholar 

  71. Ariyasu, H., Takaya, K., Tagami, T., et al. (2001). J. Clin. Endocrinol. Metab. 86, 4753–4758.

    Article  PubMed  CAS  Google Scholar 

  72. Cummings, D. E., Purnell, J. Q., Frayo, R. S., Schmidova, K., Wisse, B. R., and Weigle, D. S. (2001). Diabetes 50, 1714–1719.

    Article  PubMed  CAS  Google Scholar 

  73. Otto, B., Cuntz, U., Fruehauf, E., et al. (2001). Eur. J. Endocrinol. 145, 669–673.

    Article  PubMed  CAS  Google Scholar 

  74. Shiiya, T., Nakazato, M., Mizuta, M., et al. (2002). J. Clin. Endocrinol. Metab. 87, 240–244.

    Article  PubMed  CAS  Google Scholar 

  75. Tschop, M., Wawarta, R., Riepl, R. L., et al. (2001). J. Endocrinol. Invest. 24, RC19-RC21.

    PubMed  CAS  Google Scholar 

  76. Tschop, M., Weyer, C., Tataranni, P. A., Devanarayan, V., Ravussin, E., and Heiman, M. L. (2001). Diabetes 50, 707–709.

    Article  PubMed  CAS  Google Scholar 

  77. de Lecea, L., del Rio, J. A., Criado, J. R., et al. (1997). J. Neurosci. 17, 5868–5880.

    PubMed  Google Scholar 

  78. de Lecea, L., Ruiz-Lozano, P., Danielson, P. E., et al. (1997). Genomics 42, 499–506.

    Article  PubMed  Google Scholar 

  79. Fukusumi, S., Kitada, C., Takekawa, S., et al. (1997). Biochem. Biophys. Res. Commun. 232, 157–163.

    Article  PubMed  CAS  Google Scholar 

  80. Spier, A. D. and de Lecea, L. (2000). Brain Res. Brain Res. Rev. 33, 228–241.

    Article  PubMed  CAS  Google Scholar 

  81. Dalm, V. A., van Hagen, P. M., van Koetsveld, P. M., et al. (2003). J. Clin. Endocrinol. Metab. 88, 270–276.

    Article  PubMed  CAS  Google Scholar 

  82. de Lecea, L., Criado, J. R., Prospero-Garcia, O., et al. (1996). Nature 381, 242–245.

    Article  PubMed  Google Scholar 

  83. Kreienkamp, H. J. (1999). Results Probl. Cell Differ. 26, 215–237.

    PubMed  CAS  Google Scholar 

  84. Cone, R. D., Low, M. J., Elmquist, J. K., and Cameron, J. L. (2003). In: Williams textbook of endocrinology, 10th ed. Larsen, P. R., Reed, P., Kronenberg, H. M., Melmed, S., and Polomsky, K. S. (eds.). Elsevier Science: Philadelphia, PA.

    Google Scholar 

  85. Siehler, S., Seuwen, K., and Hoyer, D. (1998). Naunyn Schmiedebergs Arch. Pharmacol. 357, 483–489.

    Article  PubMed  CAS  Google Scholar 

  86. Vasilaki, A., Lanneau, C., Dournaud, P., de Lecea, L., Gardette, R., and Epelbaum, J. (1999). Neuroscience 88, 359–364.

    Article  PubMed  CAS  Google Scholar 

  87. Sanchez-Alavez, M., Gomez-Chavarin, M., Navarro, L., et al. (2000). Brain Res. 858, 78–83.

    Article  PubMed  CAS  Google Scholar 

  88. Deghenghi, R., Avallone, R., Torsello, A., Cuccioli, G., Ghigo, E., and Locatelli, V. (2001). J. Endocrinol. Invest. 24, RC31-RC33.

    PubMed  CAS  Google Scholar 

  89. Broglio, F., Arvat, E., Benso, A., et al. (2002). J. Clin. Endocrinol. Metab. 87, 3783–3790.

    Article  PubMed  CAS  Google Scholar 

  90. Broglio, F., Van Koetsveld, P., Benso, A., et al. (2002). J. Clin. Endocrinol. Metab. 87, 4829–4832.

    Article  PubMed  CAS  Google Scholar 

  91. Muccioli, G. (2002). In: Hormones. Body composition and physical performances. Turin, November 2002.

  92. Martinez, J., Feherentz, J. A., and Guerlavais, V. (20/12/2001). Growth hormone secretagogues, PTC-WO 01/96300 Al.

  93. Broglio, F., Boutignon, F., Benso, A., et al. (2002). J. Endocrinol. Invest. 25, RC26-RC28.

    PubMed  CAS  Google Scholar 

  94. Guerlavais, V., Boeglin, D., Heitz, A., et al. (2003). J. Med. Chem. 46, 1191–1203.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Italy

    Romano Deghenghi PhD, Fabio Broglio & Ezio Ghigo

  2. Department of Bioscience and Oncology, University of Turin, Italy

    Mauro Papotti

  3. Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Italy

    Giampiero Muccioli

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  1. Romano Deghenghi PhD
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  2. Fabio Broglio
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  3. Mauro Papotti
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  4. Giampiero Muccioli
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  5. Ezio Ghigo
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Correspondence to Romano Deghenghi PhD.

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Deghenghi, R., Broglio, F., Papotti, M. et al. Targeting the ghrelin receptor. Endocr 22, 13–18 (2003). https://doi.org/10.1385/ENDO:22:1:13

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