Advertisement

Proopiomelanocortin and the Melanocortin Peptides

  • Alex N. Eberle
Chapter
Part of the The Receptors book series (REC)

Abstract

The “melanophore stimulants” were discovered about 80 yr ago when, with surgical ablation experiments, the pituitary gland was shown to be involved in the control of skin color of amphibia. The pars intermedia was soon recognized as the origin of the biological principle, then also named “intermedin,” which induced darkening of amphibian skin (for a short historical review see ref. 1). In the 1950s, the development of an isolated frog skin bioassay by Shizume et al. (2) paved the way for the isolation (3), molecular characterization, and sequence determination of the melanocyte-stimulating hormones (MSHs; melanotropins) from pig by Lee and Lerner (4), Geschwind, et al. (5), Harris and Lerner (6) and Harris and Roos (7). In subsequent years, α-and β-melanocyte-stimulating hormones were isolated from bovine, equine, sheep, macaque, camel, dogfish, and salmon pituitary glands and their sequences determined (reviewed ref. 8). The advent of molecular cloning and sequencing techniques of the gene(s) of the melanotropin precursors made it possible to determine or confirm many more MSH sequences.

Keywords

Melanoma Cell Pituitary Gland Human Melanoma Cell Melanocortin Receptor ACTH Peptide 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lerner, A. B. (1993) The discovery of the melanotropins. Ann. N. Y. Acad. Sci. 680, 1–12.PubMedCrossRefGoogle Scholar
  2. 2.
    Shizume, K., Lerner, A. B., and Fitzpatrick, T. B. (1954) In vitro bioassay for melanocyte stimulating hormone. Endocrinology 54, 553–560.PubMedCrossRefGoogle Scholar
  3. 3.
    Lerner, A. B. and Lee, T. H. (1955) Isolation of a homogeneous melanocytestimulating hormone from hog pituitary gland. J. Am. Chem. Soc. 77, 1066–1067.CrossRefGoogle Scholar
  4. 4.
    Lee, T. H. and Lerner A. B. (1956) Isolation of melanocyte-stimulating hormone from hog pituitary gland. J. Biol. Chem. 221, 943–959.PubMedGoogle Scholar
  5. 5.
    Geschwind, I. I., Li, C. H., and Barnafi, L. (1956) Isolation and structure of melanocyte-stimulating hormone from porcine pituitary glands. J. Am. Chem. Soc. 78, 4494–4495.CrossRefGoogle Scholar
  6. 6.
    Harris, J. I. and Lerner, A. B. (1957) Amino-acid sequence of the a-melanocytestimulating hormone. Nature 179, 1346–1347.PubMedCrossRefGoogle Scholar
  7. 7.
    Harris, J. I. and Roos, P. (1959) Studies on pituitary polypeptide hormones. I. The structure of a-melanocyte-stimulating hormone from pig pituitary glands. Biochem. J. 71, 434 445.PubMedGoogle Scholar
  8. 8.
    Eberle, A. N. (1988) The Melanotropins: Chemistry, Physiology and Mechanisms of Action. Karger, Basel.Google Scholar
  9. 9.
    Bell, P. H. (1954) Purification and structure of (3-corticotropin. J. Am. Chem. Soc. 76, 5565–5567.CrossRefGoogle Scholar
  10. 10.
    Riniker, B., Sieber, P., Rittel, W., and Zuber, H. (1972) Revised amino acid sequences for porcine and human adenocorticotropic hormone. Nature New Biol. 235, 114–115.PubMedGoogle Scholar
  11. 11.
    Li, C. H., Barnafi, L., Chrétien, M., and Chung, C. (1966) Isolation and amino acid sequence of ß-LPH from sheep pituitary glands. Nature 208, 1093–1094.CrossRefGoogle Scholar
  12. 12.
    Chrétien, M., Gilardeau, C., and Li, C. H. (1972) Revised structure of sheep (3-lipotropic hormone. Int. J. Pept. Protein Res. 4, 263–265.PubMedCrossRefGoogle Scholar
  13. 13.
    Chrétien, M. and Li, C. H. (1967) Isolation, purification and characterization of γ-lipotropic hormone from sheep pituitary glands. Can. J. Biochem. 43, 1163–1174.Google Scholar
  14. 14.
    Scott, A. P., Ratcliffe, J. G., Rees, L. H., Landon, J., Bennett, H. P. J., Lowry, P. J., and McMartin, C. (1973) Pituitary peptide. Nature New Biol. 244, 65–67.PubMedGoogle Scholar
  15. 15.
    Bradbury, A. F., Smyth, D. G., Snell, C. R., and Birdsall, N. J. (1976) The C-fragment of lipotropin: an endogenous peptide with high affinity for brain opiate receptors. Nature 260, 793–795.CrossRefGoogle Scholar
  16. 16.
    Graf, L., Ronai, A. Z., Bajusz, S., Cseh, G., and Szekely, J. I. (1976) Opioid agonist activity of (3-lipotropin fragments: a possible biological lipotropin source of morphine-like substances in the pituitary. FEBS Lett. 64, 181–184.PubMedCrossRefGoogle Scholar
  17. 17.
    Li, C. H. and Chung, D. (1976) Isolation and structure of an untriakontapeptide with opiate activity from camel pituitary glands. Proc. Natl. Acad. Sci. U.S.A. 73, 1145–1148.PubMedCrossRefGoogle Scholar
  18. 18.
    Yalow, R. S. and Berson, S. A. (1971) Size heterogeneity of immunoreactive human ACTH in plasma and in extracts of pituitary glands and ACTH-producing thymoma. Biochem. Biophys. Res. Commun. 44, 439–445.PubMedCrossRefGoogle Scholar
  19. 19.
    Yalow, R. S. and Berson, S. A. (1973) Characteristics of ‘big ACTH’ in human plasma and pituitary extracts. J. Clin. Endocrinol. Metab. 36, 415–423.PubMedCrossRefGoogle Scholar
  20. 20.
    Mains, R. E., Eipper, B. A., and Ling, N. (1977) Common precursor to corticotropins and endorphins. Proc. Natl. Acad. Sci. U.S.A. 74, 3014–3018.PubMedCrossRefGoogle Scholar
  21. 21.
    Roberts, J. L. and Herbert, E. (1977) Characterization of a common precursor to corticotropin and 3-lipotropin: cell-free synthesis of the precursor and identification of corticotropin peptides in the molecule. Proc. Natl. Acad. Sci. U.S.A. 74, 4826–4830.PubMedCrossRefGoogle Scholar
  22. 22.
    Bertagna, X., Nicholson, W. E., Sorenson, G. D., Pettengill, O. S., Mount, C. D., and Orth, D. N. (1978) Corticotropin, lipotropin, and [3-endorphin production by a human non-pituitary tumor in culture: evidence for a common precursor. Proc. Natl. Acad. Sci. U.S.A. 75, 5160–5164.PubMedCrossRefGoogle Scholar
  23. 23.
    Nakanishi, S., Inoue, A., Kita, T., Nakamura, M., Chang, A. C. Y., Cohen, S. N., and Numa, S. (1979) Nucleotide sequence of cloned cDNA for bovine corticotropin-(3-lipotropin precursor. Nature 278, 423–427.PubMedCrossRefGoogle Scholar
  24. 24.
    Takahashi, A., Amemiya, Y., Sakai, M., Yasuda, Y., Suzuki, N., Sasayama, Y., and Kawauchi, H. (1998) Occurrence of four MSHs in dogfish POMC and their immunomodulating effects. Exp. Dermatol. 7, 231Google Scholar
  25. Amemiya, Y., Takahashi, A., Suzuki, N., Sasayama, Y., and Kawauchi, H. (1999) A newly characterized melanotropin in proopiomelanocortin in pituitaries of an elasmobranch, Squalus acanthias. Gen. Comp. Endocrinol., 114, 387–395.CrossRefGoogle Scholar
  26. 25.
    Scimonelli, T. and Eberle, A. N. (1987) Photoaffinity labelling of melanoma cell MSH receptors. FEBS Lett. 226, 134–138.PubMedCrossRefGoogle Scholar
  27. 26.
    Solca, F., Siegrist, W., Drozdz, R., Girard, J., and Eberle, A. N. (1989) The receptor for a-melanotropin of mouse and human melanoma cells: application of a potent a-melanotropin photoaffinity label. J. Biol. Chem. 264, 14,277–14, 281.Google Scholar
  28. 27.
    Gerst, J. E., Sole, J., Hazum, E., and Salomon, Y. (1988) Identification and characterization of melanotropin binding proteins from M2R melanoma cells by covalent photoaffinity labeling. Endocrinology 123, 1792–1797.PubMedCrossRefGoogle Scholar
  29. 28.
    Mountjoy, K. G., Robbins, L. S., Mortrud, M. T., and Cone, R. D. (1992) The cloning of a family of genes that encode the melanocortin receptors. Science 28, 1248–1251.CrossRefGoogle Scholar
  30. 29.
    Chhajlani, V. and Wikberg, J. E. (1992) Molecular cloning and expression of the human melanocyte-stimulating hormone receptor cDNA. FEBS Lett. 309, 417–420.PubMedCrossRefGoogle Scholar
  31. 30.
    Roselli-Rehfuss, L., Mountjoy, K. G., Robbins, L. S., Mortrud, M. T., Low, M. J., Tatro, J. B., Entwistle, M. L., Simerly, R. B., and Cone, R. D. (1993) Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc. Natl. Acad. Sci. U.S.A. 90, 8856–8860.PubMedCrossRefGoogle Scholar
  32. 31.
    Gantz, I., Konda, Y., Tashiro, T., Shimoto, Y., Miwa, H., Munzert, G., Watson, S. J., DelValle, J., and Yamada, T. (1993) Molecular cloning of a novel melanocortin receptor. J. Biol. Chem. 268, 8246–8250.PubMedGoogle Scholar
  33. 32.
    Gantz, I., Miwa, H., Konda, Y., Shimoto, Y., Tashiro, T., Watson, S. J., DelValle, J., and Yamada, T. (1994) Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J. Biol. Chem. 268, 15,174–15,179.Google Scholar
  34. 33.
    Chhajlani, V., Muceniece, R., and Wikberg, J. E. (1993) Molecular cloning of a novel human melanocortin receptor. Biochem. Biophys. Res. Commun. 195, 866–873.PubMedCrossRefGoogle Scholar
  35. 34.
    Gantz, I., Shimoto, Y., Konda, Y., Miwa, H., Dickinson, C. J., and Yamada, T. (1994) Molecular cloning, expression, and characterization of a fifth melanocortin receptor. Biochem. Biophys. Res. Commun. 200, 1214–1220.PubMedCrossRefGoogle Scholar
  36. 35.
    Griffon, N., Mignon, V., Facchinetti, P., Diaz, J., Schwartz, J. C., and Sokoloff, P. (1994) Molecular cloning and characterization of the rat fifth melanocortin receptor. Biochem. Biophys. Res. Commun. 200, 1007–1014.PubMedCrossRefGoogle Scholar
  37. 36.
    Labbe, O., Desarnaud, F., Eggerickx, D., Vassart, G., and Parmentier, M. (1994) Molecular cloning of a mouse melanocortin-5 receptor gene widely expressed in peripheral tissues. Biochemistry 33, 4543–4549.PubMedCrossRefGoogle Scholar
  38. 37.
    Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J., and Cone, R. D. (1997) Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 385, 165–168.PubMedCrossRefGoogle Scholar
  39. 38.
    Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., Smith, F. J., Campfield, L.A., and Burn, P. (1997) Targeted disruption of the melanocortin4 receptor results in obesity in mice. Cell 88, 131–141.PubMedCrossRefGoogle Scholar
  40. 39.
    Boston, B. A., Blaydon, K. M., Varnerin, J., and Cone, R. D. (1997) Independent and additive effects of central POMC and leptin pathways on murine obesity. Science 278, 1641–1644.PubMedCrossRefGoogle Scholar
  41. 40.
    Tritos, N. A., Vicent, D., Gillette, J., Ludwig, D. S., Flier, E. S., and Maratos-Flier, E. (1998). Functional interactions between melanin-concentrating hormone, neuropeptide Y, and anorectic neuropeptides in the rat hypothalamus. Diabetes 47, 1687–1692.PubMedCrossRefGoogle Scholar
  42. 41.
    Bennett, H. P. J. (1986) Use of ion-exchange Sep-Pak cartridges in the batch fractionation of pituitary peptides. J. Chromatogr. 359, 383–390.PubMedCrossRefGoogle Scholar
  43. 42.
    Bennett, H. P. J. (1986) Biosynthetic fate of the amino-terminal fragment of proopiomelanocortin within the intermediate lobe of the mouse pituitary. Peptides 7, 615–622.PubMedCrossRefGoogle Scholar
  44. 43.
    Van Strien, F. J., Jesperson, S., van der Greef, J., Jenks, B. G., and Roubos, E. W. (1996) Identification of POMC processing products in single melanotrope cells by matrix-assisted laser desorption/ionization mass spectrometry. FEBS Lett. 379, 165–170.PubMedCrossRefGoogle Scholar
  45. 44.
    Rudman, D., Chawla, R. K., and Hollins, B. M. (1979) N,O-Di-acetylserine’a-melanocyte-stimulating hormone, a naturally occurring melanotropic peptide. J. Biol. Chem. 254, 10102–10108.PubMedGoogle Scholar
  46. 45.
    Geschwind, I. I. (1959) Species variation in protein and polypeptide hormones, in Comparative Endocrinology ( Grobman, A., ed.), Wiley, New York pp. 421–443.Google Scholar
  47. 46.
    Dixon, J. S. and Li, C. H. (1960) The isolation and structure of a-melanocytestimulating hormone from horse pituitaries. J. Am. Chem. Soc. 82, 4568–4572.CrossRefGoogle Scholar
  48. 47.
    Lee, T. H., Lerner, A. B., and Buettner-Janusch, V. (1961) The isolation and structure of a-and f3-melanocyte-stimulating hormones from monkey pituitary glands. J. Biol. Chem. 236, 1390–1394.PubMedGoogle Scholar
  49. 48.
    Scott, A. P., Lowry, P. J., Ratcliffe, J. G., Rees, L. H., and Landon, J. (1974) Corticotrophin-like peptides in the rat pituitary. J. Endocrinol. 61, 355–367.PubMedCrossRefGoogle Scholar
  50. 49.
    Li, C. H., Danho, W. O., Chung, D., and Rao, A. J. (1975) Isolation, characterization, and amino acid sequence of melanotropins from camel pituitary glands. Biochemistry 14, 947–952.PubMedCrossRefGoogle Scholar
  51. 50.
    Lee, T. H., Lerner, A. B., and Buettner-Janusch, V. (1963) Melanocyte-stimulating hormones from sheep pituitary glands. Biochim. Biophys. Acta 71, 706–709.PubMedCrossRefGoogle Scholar
  52. 51.
    Notake, M., Tobimatsu, T., Watanabe, Y., Takahashi, H., Mishina, M., and Numa, S. (1983) Isolation and characterization of the mouse corticotropin-(3-lipotropin precursor gene and a related pseudogene. FEBS Lett. 156, 67–71.PubMedCrossRefGoogle Scholar
  53. 52.
    Keightley, M. C., Funder, J. W., and Fuller, P. J. (1991) Molecular cloning and sequencing of a guinea pig pro-opiomelanocortin cDNA. Mol. Cell. Endocrinol. 82, 89–98.PubMedCrossRefGoogle Scholar
  54. 53.
    Tonon, M. C., Desrues, L., Lazure, C., Jenks, B. G., Chrétien, M., and Vaudry, H. (1989) Melanin concentrating hormone. V. Isolation and characterization of a-melanocyte-stimulating hormone from frog pituitary glands. Life Sci. 45, 1155–1161.PubMedCrossRefGoogle Scholar
  55. 54.
    Martens, G. J. M., Civelli, O., and Herbert, E. (1985) Nucleotide sequence of cloned cDNA for pro-opiomelanocortin in the amphibian Xenopus laevis. J. Biol. Chem. 260, 13,685–13,689.Google Scholar
  56. 55.
    Follenius, E., van Dorsselaer, A., and Meunier, A. (1986) Proportions of mono-and diacetylated forms of a-MSH in individual neurointermediate lobe extracts of Cyprinus carpio L. Comp. Biochem. Phyisol. 184, 315–317.Google Scholar
  57. 56.
    Kawauchi, H. and Muramoto, K. (1979) Isolation and primary structure of melanotropins from salmon pituitary glands. Int. J “ ept. Protein Res. 14, 373–374.CrossRefGoogle Scholar
  58. 57.
    Kawauchi, H., Adachi, Y., and Tsubokawa, M. (1980) Occurrence of a new melanocyte stimulating hormone in the salmon pituitary gland. Biochem. Biophys. Res. Commun. 96, 1508–1517.PubMedCrossRefGoogle Scholar
  59. 58.
    Salbert, G., Chauveau, I., Bonnec, G., Valotaire, Y., and Jego, P. (1992) One of the two trout proopiomelanocortin messenger RNAs potentially encodes new peptides. Mol. Endocrinol. 6, 1605–1613.PubMedCrossRefGoogle Scholar
  60. 59.
    Amemiya, Y., Takahashi, A., Dores, R. M., and Kawauchi, H. (1997) Sturgeon proopiomelanocortin has a remnant of y-melanotropin. Biochem. Biophys. Res. Commun. 230, 452–456.PubMedCrossRefGoogle Scholar
  61. 60.
    Smith, T. R., Rubin, D., Dores, R. M., Youson, J., and Marra, L. (1996) GENBANK, accession U59910.Google Scholar
  62. 61.
    Arends, R. J., Vermeer, H., Martens, G. J., Leunissen, J. A., Wnedelaar Bonga, S. E., and Flik, G. (1998) Cloning and expression of two proopiomelanocortin mRNAs in the common carp (Cyprinus carpo L.). Mol. Cell. Endocrinol. 143, 23–31.PubMedCrossRefGoogle Scholar
  63. 62.
    Okuta, A., Ando, H., Ueda, H., and Urano, A. (1996) Two types of cDNAs encoding proopiomelanocortin of sockeye salmon, Oncorhynchus keta. Zoolog. Sci. 13, 421–427.CrossRefGoogle Scholar
  64. 63.
    Bennett, H. P. J., Lowry, P. J., McMartin, C., and Scott, A. P. (1974) Structural studies of a-melanocyte-stimulating hormone and a novel (3-melanocyte-stimulating hormone from the neurointermediate lobe of the pituitary of the dogfish Squalus acanthias. Biochem. J. 141, 439–444.Google Scholar
  65. 64.
    Takahashi A., Amemiya, Y., Nozaki, M., Sower, S. A., Joss, J., Gorbman, A., and Kawauchi, H. (1995) Isolation and characterization of melanotropins from lamprey pituitary glands. Int. J. Pept. Protein Res. 46, 197–204.PubMedCrossRefGoogle Scholar
  66. 65.
    Heinig, J. A., Keeley, F. W., Robson, P., Sower, S. A., and Yourson, J. H. (1995) The appearance of proopiomelanocortin early in vertebrate evolution: cloning and sequencing of POMC from a lamprey pituitary cDNA library. Gen. Comp. Endocrinol. 99, 137–144.PubMedCrossRefGoogle Scholar
  67. 66.
    Takahashi, A., Amemiya, Y., Sarashi, M., Sower, S. A., and Kawauchi, H. (1995) Melanocortin and corticotropin are encoded on two distinct genes in the lamprey, the earliest evolved extant vertebrate. Biochem. Biophys. Res. Commun. 213, 490–498.PubMedCrossRefGoogle Scholar
  68. 67.
    Vaudry, H., Jenks, B. G., and Overbeeke, A. P. (1983) The frog pars intermedia contains only the non-acetylated form of a-MSH: acetylation to generate a-MSH occurs during the release process. Life Sci. 33, 97–100.PubMedCrossRefGoogle Scholar
  69. 68.
    Van Strien, F. J. C., Galas, L., Jenks, B. G., and Roubos, E. W. (1995) Differential acetylation of POMC-derived peptides in the pituitary gland of Xenopus laevis in relation to background adaptation. J. Endocrinol. 146, 159–167.PubMedCrossRefGoogle Scholar
  70. 69.
    Ellerkmann, E., Porter, T. E., Nagy, G. M., and Frawley, L. S. (1992) N-Acetylation is required for the lactotrope recruitment activity of a-melanocyte-stimulating hormone and 13-endorphin. Endocrinology 131, 566–570.PubMedCrossRefGoogle Scholar
  71. 70.
    Bundel, D. T., Conlon, J. M., Chartrel, N., Tonon, M. C., and Vaudry, H. (1992) Isolation and structural characterization of peptides related to a-and y-melanocytestimulating hormone (MSH) from the frog brain. Brain Res. Mol. Brain Res. 15, 1–7.CrossRefGoogle Scholar
  72. 71.
    Bertagna, X., Seidah, N., Massias, J. F., Lenne, F., Luton, J. P., Girard, F., and Chrétien, M. (1989) Microsequencing evidence for the maturation of human proopiomelanocortin into an 18 amino acid 3-melanocyte stimulating hormone [h f3-MSH(5–22)1 in nonpituitary tissue. Peptides 10, 83–87.PubMedCrossRefGoogle Scholar
  73. 72.
    Harris, J. I. and Roos, P. (1956) Amino-acid sequence of a melanophore stimulating peptide. Nature 178, 90.PubMedCrossRefGoogle Scholar
  74. 73.
    Dixon, J. S. and Li, C. H. (1961) The isolation and structure of 13-melanocytestimulating hormone from horse pituitary gland. Gen. Comp. Endocrinol. 1, 161–169.PubMedCrossRefGoogle Scholar
  75. 74.
    Geschwind, I. I., Li, C. H., and Barnafi, L. (1957) The isolation, characterization and amino acid sequence of a melanocyte-stimulating hormone from bovine pituitary glands. J. Am. Chem. Soc. 79, 6394–6401.CrossRefGoogle Scholar
  76. 75.
    Drouin, J., Chamberland, M., Charron, J., Jeannotte, L., and Nemer, M. (1985) Structure of the rat pro-opiomelanocortin (POMC) gene. FEBS Lett. 193, 54–58.PubMedCrossRefGoogle Scholar
  77. 76.
    Hilario, E., Lihrmann, I., and Vaudry, H. (1990) Characterization of the cDNA encoding proopiomelanocortin in the frog Rana ridibunda. Biochem. Biophys. Res. Commun. 173, 653–659.PubMedCrossRefGoogle Scholar
  78. 77.
    Pan, F. M. and Chang W. C. (1989) Nucleotide sequence of bullfrog proopiomelanocortin cDNA. Nucleic Acids Res. 17, 58–43.Google Scholar
  79. 78.
    Kawauchi, H., Adachi, Y., and Ishizuka, B. (1980) Isolation and structure of another 3-melanotropin from salmon pituitary glands. Int. J. Pept. Protein Res. 16, 79–82.PubMedCrossRefGoogle Scholar
  80. 79.
    Love, R. M. and Pickering, B. T. (1974) A 13-MSH in the pituitary gland of the spotted dogfish (Scyliorhinus canicula): isolation and structure. Gen. Comp. Endocrinol. 24, 398–404.PubMedCrossRefGoogle Scholar
  81. 80.
    Scott, A. P. and Lowry, P. J. (1974) Adenocorticotrophic and melanocyte-stimulating peptides in the human pituitary. Biochem. J. 139, 593–602.PubMedGoogle Scholar
  82. 81.
    Bertagna, X. (1994) Proopiomelanocortin-derived peptides. Endocrinol. Metab. Clin. North Am. 23, 467–485.PubMedGoogle Scholar
  83. 82.
    Kitahara, N., Nishizawa, T., Iida, K., Okazaki, H., Andoh, T., and Soma, G. I. (1988) Absence of a y-melanocyte-stimulating hormone sequence in proopiomelanocortin mRNA of chum salmon Oncorhynchus keta. Comp. Biochem. Physiol. [B] 91, 365–370.Google Scholar
  84. 83.
    Böhlen, P., Esch, F., Shibasaki, T., Baird, A., Ling, N., and Guillemin, R. (1981) Isolation and characterization of a y-melanotropin-like peptide from bovine neurointermediate pituitary. FEBS Lett. 128, 67–70.PubMedCrossRefGoogle Scholar
  85. 84.
    Rouillé, Y., Michel, G., Chauvet, M. T., Chauvet, J., and Acher, R. (1989) Particular proecessing of pro-opiomelanocortin in Xenopus laevis intermediate pituitary: sequencing of a-and {3-melanocyte stimulating hormones. FEBS Lett. 245, 215–218.PubMedCrossRefGoogle Scholar
  86. 85.
    Chauvet, J., Michel, G., Rouillé, Y., Chauvet, M. T., and Acher, R. (1991) Study of frog (Rana esculenta) proopiomelanocortin processing in the intermediate pituitary. Identification of a-melanotropin, f3-melanotropin, Lys-y-melanotropin, and corticotropin-like intermediate lobe peptide. Int. J. Pept. Protein Res. 37, 236–240.PubMedCrossRefGoogle Scholar
  87. 86.
    Van Strien, F. J., Devreese, B., van Beeumen, J., Roubos, E. W., and Jenks, B. G. (1995) Biosynthesis and processing of the N-terminal part of proopiomelanocortin in Xenopus laevis: characterization of y-MSH peptides. J. Neuroendocrinol. 7, 807–815.PubMedCrossRefGoogle Scholar
  88. 87.
    Salzet, M., Wattez, C., Bulet, P., and Malecha, J. (1994) Isolation and structural characterization of a novel peptide related to y-melanocyte stimulating hormone from the brain of the leech Theromyzon tessulatum. FEBS Lett. 348, 102–106.PubMedCrossRefGoogle Scholar
  89. 88.
    Bennett, H. P. J., Seidah, N. G., Benjannet, S., Solomon, S., and Chrétien, M. (1986) Reinvestigation of the disulfide bridge arrangement in human proopiomelanocortin N-terminal segment (hNT 1–76). Int. J. Pept. Protein Res. 27, 306–313.PubMedCrossRefGoogle Scholar
  90. 89.
    Patel, P. D., Sherman, T. G., and Watson, S. J. (1988) Characterization of proopiomelanocortin cDNA from the Old World monkey, Macaca nemestrina. DNA 7, 627–635.CrossRefGoogle Scholar
  91. 90.
    Seger, M. A. and Bennett, H. P. J. (1986) Structure and bioactivity of the amino-terminal fragment of proopiomelanocortin. J. Steroid Biochem. 25, 703–710.PubMedCrossRefGoogle Scholar
  92. 91.
    Gen, K., Hirai, T., Kato, T., and Kato, Y. (1994) Presence of the same transcript of proopiomelanocortin (POMC) genes in the porcine anterior and intermediate pituitary lobes. Mol. Cell. Endocrinol. 103, 101–108.PubMedCrossRefGoogle Scholar
  93. 92.
    Browne, C. A., Bennett, H. P. J., and Solomon, S. (1981) The isolation and characterization of y3-melanotropin from the neurointermediate lobe of the rat pituitary. Biochem. Biophys. Res. Commun. 100, 336–343.PubMedCrossRefGoogle Scholar
  94. 93.
    Bennett, H. P. J. (1986) Biosynthetic fate of the amino-terminal fragment of proopiomelanocortin within the intermediate lobe of the mouse pituitary. Peptides 7, 615–622.PubMedCrossRefGoogle Scholar
  95. 94.
    McLean, C. and Lowry, P. J. (1981) Natural occurrence but lack of melanotropic activity of y-MSH in fish. Nature 290, 341–343.PubMedCrossRefGoogle Scholar
  96. 95.
    Schwyzer, R. (1977) ACTH: a short introductory review. Ann. N.Y. Acad. Sci. 297, 3–26.PubMedCrossRefGoogle Scholar
  97. 96.
    Martens, G. J. M. (1986) Expression of two proopiomelanocortin genes in the pituitary gland of Xenopus laevis: complete structures of the two preprohormones. Nucleic Acids Res. 14, 3791–3798.PubMedCrossRefGoogle Scholar
  98. 97.
    Soma, G. I., Kitahara, N., Nishizawa, T., Nanami, H., Kotake, C., Okazaki, H., and Andoh, T. (1984) Nucleotide sequence of a cloned cDNA for proopiomelanocortin precursor of chum salmon, Onchorynchus keta. Nucleic Acids Res. 12, 8029–8041.CrossRefGoogle Scholar
  99. 98.
    Boileau, G., Barbeau, C., Jeannotte, L., Chrétien, M., and Drouin, J. (1983) Complete structure of the porcine pro-opiomelanocortin mRNA derived from the nucleotide sequence of cloned cDNA. Nucleic Acids Res. 11, 8063–8071.PubMedCrossRefGoogle Scholar
  100. 99.
    Chang, A. C., Cochet, M., and Cohen, S. N. (1980) Structural organization of human genomic DNA encoding the pro-opiomelanocortin peptide. Proc. Natl. Acad. Sci. U.S.A. 77, 4890–4894.PubMedCrossRefGoogle Scholar
  101. 100.
    Kitahara, N., Nishizawa, T., Iida, K., Okazaki, H., Andoh, T., and Soma, G. (1988) Absence of y-melanocyte-stimulating hormone mRNA of chum salmon Oncorhynchus keta. Comp. Biochem. Physiol. 91, 365–370.Google Scholar
  102. 101.
    Maier, R., Barthe, P. L., Schenkel-Hulliger, L., and Desaulles, P. A. (1971) The biological activity of (1-D-serine, 17–18-dilysine)-corticotrophin-(1–18)-octadecapeptideamide. Acta Endocrinol. 68, 458–466.PubMedGoogle Scholar
  103. 102.
    Geiger, R. (1971) Synthese eines Heptadecapeptids mit hoher adrenocorticotroper Wirkung. Liebigs Ann. Chem. 750, 165–171.CrossRefGoogle Scholar
  104. 103.
    Roubos, E. W. (1997) Background adaptation by Xenopus laevis: a model for studying neuronal information processing in the pituitary pars intermedia. Comp. Biochem. Physiol. A Physiol. 118, 533–550.PubMedCrossRefGoogle Scholar
  105. 104.
    Desrues, L., Tonon, M. C., Leprince, J., Vaudry, H., and Conlon, J. M. (1998) Isolation, primary structure, and effects on a-melanocyte-stimulating hormone release of frog neurotensin. Endocrinology 139, 4140–4146.PubMedCrossRefGoogle Scholar
  106. 105.
    Chartrel, N., Conlon, J. M., Danger, J. M., Fournier, A., Tonon, M. C., and Vaudry, H. (1992) Characterization of melanotropin-release-inhibiting factor (melanostatin) from frog brain: homology with human neuropeptide Y. Proc. Natl. Acad. Sci. U.S.A. 88, 3862–3866.CrossRefGoogle Scholar
  107. 106.
    Mor, A., Chartrel, N., Vaudry, H., and Nicolas, P. (1994) Skin peptide tyrosine-tyrosine, a member of the pancreatic polypeptide family: isolation, structure, synthesis, and endocrine activity. Proc. Natl. Acad. Sci. U.S.A. 91, 10,295–10,299.Google Scholar
  108. 107.
    Wakamtsu, K., Graham, A., Cook, D., and Thody, A. J. (1997) Characterization of ACTH peptides in human skin and their activation of the melanocortin-1 receptor. Pigment Cell Res. 10, 288–297.CrossRefGoogle Scholar
  109. 108.
    Thody, A. J. and Graham, A. (1998) Does a-MSH have a role in regulating skin pigmentation in humans? Pigment Cell Res. 11, 265–274.PubMedCrossRefGoogle Scholar
  110. 109.
    Furumura, M., Sakai, C., Abdel-Malek, Z., Barsh, G. S., and Hearing, V. J. (1996) The interaction of agouti signal protein and melanocyte stimulating hormone to regulate melanin formation in mammals. Pigment Cell Res. 9, 191–203.PubMedCrossRefGoogle Scholar
  111. 110.
    Aberdam, E., Bertolotto, C., Sviderskaya, E. V., de Thillot, V., Hemesath, T. J., Fisher, D. E., Bennett, D. C., Ortonne, J. P., and Ballotti, R. (1998) Involvement of microphthalmia in the inhibition of melanocyte lineage differentiation and of melanogenesis by agouti signal protein. J. Biol. Chem. 273, 19560–19565.PubMedCrossRefGoogle Scholar
  112. 111.
    Cone, R. D., Lu, D., Koppula, S., Vage, D. I., Klungland, H., Boston, B., Chen, W., Orth, D. N., Pouton, C., and Kesterson, R. A. (1996) The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation. Recent Progr. Horm. Res. 51, 287–317.PubMedGoogle Scholar
  113. 112.
    Smith, R., Healy, E., Siddiqui, S., Flanagan, N., Steijlen, P. M., Rosdahl, I., Jacques, J. P., Rogers, S., Turner, R., Jackson, I. J., Birch-Machin, M. A., and Rees, J. L. (1998) Melanocortin I receptor variants in an Irish population. J. Invest. Dermatol. 111, 119–122.PubMedCrossRefGoogle Scholar
  114. 113.
    Kijas, J. M., Wales, R., Tornsten, A., Chardon, P., Moller, M., and Andersson, L. (1998) Melanocortin receptor 1 (MC 1-R) mutations and coat color in pigs. Genetics 150, 1177–1185.PubMedGoogle Scholar
  115. 114.
    Funasaka, Y., Chakraborty, A. K., Hayashi, Y., Komoto, M. Ohashi, A., Nagahama, M., Inoue, Y., Pawelek, J., and Ichihashi, M. (1998) Modulation of melanocytestimulating hormone receptor expression on normal human melanocytes: evidence for a regulatory role of ultraviolet B, interleukin-1 a, interleukin-13, endothelin-1 and tumour necrosis factor-a. Br. J. Dermatol. 139, 216–224.PubMedCrossRefGoogle Scholar
  116. 115.
    Loir, B., Bouchard, B., Morandini, R., Del Marmol, V., Deraemaecker, R., GarciaBorron, J. C., and Ghanem, G. (1997) Immunoreactive a-melanotropin as an autocrine effector in human melanoma cells. Eur. J. Biochem. 244, 923–930.PubMedCrossRefGoogle Scholar
  117. 116.
    Morandini, R., Boeynaems, J. M., Hedley, S. J., MacNeil, S., and Ghanem, G. (1998) Modulation of ICAM-1 expression by a-MSH in human melanoma cells and melanocytes. J. Cell Physiol. 175, 276–282.PubMedCrossRefGoogle Scholar
  118. 117.
    Scott, G., Cassidy, L., and Abdel-Malek, Z. (1997) a-Melanocyte-stimulating hormone and endothelin-1 have opposite effects on melanocyte adhesion, migration, and pp125FAK phosphorylation. Exp. Cell Res. 237, 19–28.PubMedCrossRefGoogle Scholar
  119. 118.
    Ghanem, G., Loir, B., Hadley, M., Abdel-Malek, Z., Libert, A., Del Marmol, V., Lejeune, F., Lozano, J., and Garcia-Borron, J. C. (1992) Partial characterization of IR-a-MSH peptides found in melanoma tumors. Peptides 13, 989–994.PubMedCrossRefGoogle Scholar
  120. 119.
    Schauer, E., Trautinger, F., Kock, A., Schwarz, A., Bhardwaj, R., Simon, M., Ansel, J. C., Schwarz, T., and Luger, T. A. (1994) Proopiomelanocortin-derived peptides are synthesized and released by human keratinocytes. J. Clin. Invest. 93, 2258–2262.PubMedCrossRefGoogle Scholar
  121. 120.
    Luger, T. A., Scholzen, T., and Grabbe, S. (1997) The role of a-melanocytestimulating hormone in cutaneous biology. J. Invest. Dermatol. Symp. Proc. 2, 87–93.CrossRefGoogle Scholar
  122. 121.
    Hartmeyer, M., Scholzen, T., Becher, E., Bhardwaj, R. S., Schwarz, T., and Luger, T. A. (1997) Human dermal microvascular endothelial cells express the melanocortin receptor type 1 and produce increased levels of IL-8 upon stimulation with a-melanocyte-stimulating hormone. J. Immunol. 159, 1930–1937.PubMedGoogle Scholar
  123. 122.
    Strand, F. L., Williams, K. A., Alves, S. E., Antonawich, F. J., Lee, T. S., Lee, S. J., Kume, J., and Zuccarelli, LA. (1994) Melanocortins as factors in somatic neuromuscular growth and regrowth. Pharmacol. Ther. 62, 1–27.PubMedCrossRefGoogle Scholar
  124. 123.
    Zohar, M. and Salomon, Y. (1992) Melanocortins stimulate proliferation and induce morphological changes in cultured rat astrocytes by distinct transducing mechanisms. Brain Res. 576, 49–58.PubMedCrossRefGoogle Scholar
  125. 124.
    Joosten, E. A., Verhaagh, S., Martin, D., Robe, P., Franzen, R., Hooiveld, M., Doornbos, R., Bar, P. R., and Moonen, G. (1996) a-MSH stimulates neurite outgrowth of neonatal rat corticospinal neurons in vitro. Brain Res. 736, 91–98.PubMedCrossRefGoogle Scholar
  126. 125.
    Lichtensteiger, W., Hanimann, B., Siegrist, W., and Eberle, A. N. (1996) Region-and stage-specific patterns of melanocortin receptor ontogeny in rat central nervous system, cranial nerve ganglia and sympathetic ganglia. Brain Res. Dev. Brain Res. 22, 93–110.CrossRefGoogle Scholar
  127. 126.
    Kistler-Heer, V., Lauber, M. E., and Lichtensteiger, W. (1998) Different developmental patterns of melanocortin MC3 and MC4 receptor mRNA: predominance of MC4 in fetal rat nervous system. J. Neuroendocrinol. 10, 133–146.PubMedCrossRefGoogle Scholar
  128. 127.
    De Wied, D. and Ree, J. M. (1989) Neuropeptides: animals behaviour and human psychopathology. Eur. Arch. Psychiatry Neurol. Sci. 238, 323–331.PubMedCrossRefGoogle Scholar
  129. 128.
    Pitsikas, N., Spruijt, B. M., Algeri, S., and Gispen, W. H. (1990) The ACTH/MSH (4–9) analog Org2766 improves retrieval of information after a fimbria fornix transection. Peptides 11, 911–914.PubMedCrossRefGoogle Scholar
  130. 129.
    Von Frijtag, J. C., Croiset, G., Gispen, W. H., Adan, R. A., and Wiegant, V. M. (1998) The role of central melanocortin receptors in the activation of the hypothalamus-pituitary-adrenal-axis and the induction of excessive grooming. Br. J. Pharmacol. 123, 1503–1508.CrossRefGoogle Scholar
  131. 130.
    Steiger, A. and Holsboer, F. (1997) Neuropeptides and human sleep. Sleep 20, 1038–1052.PubMedGoogle Scholar
  132. 131.
    Arborelius, L., Owens, M. J., Plotsky, P. M., and Nemeroff, C. B. (1999) The role of corticotropin-releasing factor in depression and anxiety disorders. J. Endocrinol. 160, 1–12.PubMedCrossRefGoogle Scholar
  133. 132.
    Lichtensteiger, W. and Monnet, F. (1979) Differential response of dopamine neurons to a-melanotropin and analogues in relation to their endocrine and behavioural potency. Life Sci. 25, 2079–2087.PubMedCrossRefGoogle Scholar
  134. 133.
    Shimida, M., Tritos, N. A., Lowell, B. B., Flier, J. S., and Maratos-Flier, E. (1998) Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature 396, 670–674.CrossRefGoogle Scholar
  135. 134.
    Baker, B. I. (1993) The role of melanin-concentrating hormone in color change. Ann. N. Y. Acad. Sci. 680, 279–289.PubMedCrossRefGoogle Scholar
  136. 135.
    Krude, H., Biebermann, H., Luck, W., Horn, R., Brabant, G., and Gruters, A. (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat. Genet. 19, 155–157.PubMedCrossRefGoogle Scholar
  137. 136.
    Ng, T. B. (1990) Studies on hormonal regulation of lipolysis and lipogenesis in fat cells of various mammalian species. Comp. Biochem. Physiol. [B] 97, 441–446.Google Scholar
  138. 137.
    Liakos, P., Chambaz, E. M., Feige, J. J., and Defaye, G. (1998) Expression of ACTH receptors (MC2-R and MC5-R) in the glomerulosa and the fasciculatareticularis zones of bovine adrenal cortex. Endocr. Res. 24, 427–432.PubMedCrossRefGoogle Scholar
  139. 138.
    Lipton, J. M. and Clark, W. G. (1986) Neurotransmitters in temperature control. Ann. Rev. Physiol. 48, 613–623.CrossRefGoogle Scholar
  140. 139.
    Huang, Q. H., Hruby, V. J., and Tatro, J. B. (1998) Systemic a-MSH suppresses LPS fever via central melanocortin receptors independently of its suppression of corticosterone and IL-6 release. Am. J. Physiol. 275, R524 - R530.PubMedGoogle Scholar
  141. 140.
    Catania, A. and Lipton, J. M. (1998) Peptide modulation of fever and inflammation within the brain. Ann. N. Y. Acad. Sci. 856, 62–68.PubMedCrossRefGoogle Scholar
  142. 141.
    Harbour, D. V., Galin, F. S., Hughes, T. K., Smith, E. M., and Blalock, J. E. (1991) Role of leukocyte-derived pro-opiomelanocortin peptides in endotoxic shock. Circ. Shock 35, 181–191.PubMedGoogle Scholar
  143. 142.
    Lysons, P. D. and Blalock, J. E. (1997) Pro-opiomelanocortin gene expression and protein processing in rat mononuclear leukocytes. J. Neuroimmunol. 78, 47–56.CrossRefGoogle Scholar
  144. 143.
    Clarke, B. L., Moore, D. R., and Blalock, J. E. (1994) Adrenocorticotropic hormone stimulates a transient calcium uptake in rat lymphocytes. Endocrinology 135, 1780–1786.PubMedCrossRefGoogle Scholar
  145. 144.
    Bhardwaj, R. S., Schwarz, A., Becher, E., Mahnke, K., Aragane, Y., Schwarz, T., and Luger, T. A. (1996) Pro-opiomelanocortin-derived peptides induce IL-10 production in human monocytes. J. Immunol. 156, 2517–2521.PubMedGoogle Scholar
  146. 145.
    Bhardwaj, R. S., Becher, E., Mahnke, K., Hartmeier, M., Schwarz, T., Scholzen, T., and Luger, T. A. (1997) Evidence for the differential expression of functional a-melanocyte-stimulating hormone receptor MC-1 on human monocytes. J. Immunol. 158, 3378–3384.PubMedGoogle Scholar
  147. 146.
    Buggy, J. J. (1998) Binding of a-melanocyte-stimulating hormone to its G-proteincoupled receptor on B-lymphocytes activates the Jak/STAT pathway. Biochem. J. 331, 211–216.PubMedGoogle Scholar
  148. 147.
    Bilfinger, T. V., Hughes, T. K., Rodriguez, M., Glass, R., Casares, F., and Stefano, G. B. (1996) Hyperstimulation of leukocytes by plasma from cardiopulmonary bypass patients is diminished by a-MSH pretreatment. Int. J. Cardiol. 53, Suppl., S47 - S53.PubMedCrossRefGoogle Scholar
  149. 148.
    Leiba, H., Garty, N. B., Schmidt-Sole, J., Piteman, O., Azrad, A., and Salomon, Y. (1990) The melanocortin receptor in the rat lacrimal gland: a model system for the study of MSH (melanocyte-stimulating hormone) as a potential neurotransmitter. Eur. J. Pharmacol. 181, 71–82.PubMedCrossRefGoogle Scholar
  150. 149.
    Tatro, J. B. and Reichlin, S. (1987) Specific receptors for a-melanocyte-stimulating hormone are widely distributed in tissue of rodents. Endocrinology 121, 1900–1907.PubMedCrossRefGoogle Scholar
  151. 150.
    Chen, W., Kelly, M. A., Opitz-Araya, X., Thomas, R. E., Low, M. J., and Cone, R. D. (1997) Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell 91, 789–798.PubMedCrossRefGoogle Scholar
  152. 151.
    Van der Kraan, M., Adan, R. A., Entwistle, M. L., Gispen, W. H., Burbach, J. P., and Tatro, J. B. (1998) Espression of melanocortin-5 receptor in secretory epithelia supports a functional role in exocrine and endocrine glands. Endocrinology 139, 2348–2355.PubMedCrossRefGoogle Scholar
  153. 152.
    Versteeg, D. H., van Bergen, P., Adan, R. A., and de Wildt, D. J. (1998) Melanocortins and cardiovascular regulation. Eur. J. Pharmacol. 360, 1–14.PubMedCrossRefGoogle Scholar
  154. 153.
    Mayan, H., Ling, K. T., Lee, E. Y., Wiedemann, E., Kalinyak, J. E., and Humphreys, M. H. (1996) Dietary sodium intake modulates pituitary proopiomelanocortin mRNA abundance. Hypertension 28, 244–249.PubMedCrossRefGoogle Scholar
  155. 154.
    Van Bergen, P., Janssen, P. M., Hoogerhout, P., De Wildt, D. J., and Versteeg, D. H. (1995) Cardiovascular effects of y-MSH/ACTH-like peptides: structure-activity relationships. Eur. J. Pharmacol. 294, 795–803.PubMedCrossRefGoogle Scholar
  156. 155.
    Gruber, K. A. and Callahan, M. F. (1989) ACTH-(4–10) through y-MSH: evidence for a new class of central autonomic nervous system-regulating peptides. Am. J. Physiol. 257, R681–694.PubMedGoogle Scholar
  157. 156.
    Van Bergen, P., Van der Vaart, J. G., Kasbergen, C. M., Versteeg, D. H., and De Wildt, D. J. (1997) Structure-activity analysis for the effects of y-MSH/ACTH-like peptides on cerebral hemodynamics in rats. Eur.,1. Pharmacol. 318, 357–368.CrossRefGoogle Scholar
  158. 157.
    Valentin, J. P., Wiedemann, E., and Humphreys, M. H. (1993) Natriuretic properties of melanocyte-stimulating hormones. J. Cardiovasc. Pharmacol. 22, Suppl. 2, S114 - S118.Google Scholar
  159. 158.
    Nunez, L. and Frawley, L. S. (1998) a-MSH potentiates the responsiveness of mammotropes by increasing Cat+ entry. Am. J. Physiol. 274, E971 - E977.PubMedGoogle Scholar
  160. 159.
    Bar-Ilan, A., Savion, N., and Naveh, N. (1992) a-Melanocyte-stimulating hormone (a-MSH) enhances eicosanoid production by bovine retinal pigment epithelium. Prostaglandins 43, 31–44.PubMedGoogle Scholar
  161. 160.
    Zamir, E. (1997) Central serous retinopathy associated with adrenocorticotrophic hormone therapy: a case report and a hypothesis. Graefes Arch. Clin. Exp. Ophthalmol. 235, 339–344.PubMedCrossRefGoogle Scholar
  162. 161.
    Vanetti, M., Schonrock, C., Meyerhof, W., and Hollt, V. (1994) Molecular cloning of a bovine MSH receptor which is highly expressed in the testis. FEBS Lett. 348, 268–272.PubMedCrossRefGoogle Scholar
  163. 162.
    Durando, P. E. and Celis, M. E. (1998) In vitro effect of a-MSH administration on steroidogenesis of prepurbertal ovaries. Peptides 19, 667–675.PubMedCrossRefGoogle Scholar
  164. 163.
    Castrucci, A. M., Almeida, A. L., Al-Obeidi, F. A., Hadley, M. E., Hruby, V. J., Staples, D. J., and Sawyer, T. K. (1997) Comparative biological activities of a-MSH antagonists in vertebrate pigment cells. Gen. Comp. Endocrinol. 105, 410–416.PubMedCrossRefGoogle Scholar
  165. 164.
    Chluba-de Tapia, J., Bagutti, C., Cotti, R., and Eberle, A. N. (1996) Induction of constitutive melanogenesis in amelanotic mouse melanoma cells by transfection of the human melanocortin-1 receptor gene. J. Cell Sci. 109, 2023–2030.Google Scholar
  166. 165.
    Quillan, J. M., Jayawickreme, C. K., and Lerner, M. R. (1995) Combinatorial diffusion assay used to identify topically active melanocyte-stimulating hormone receptor antagonists. Proc. Natl. Acad. Sci. U.S.A. 92, 2894–2898.PubMedCrossRefGoogle Scholar
  167. 166.
    Chen, W., Shields, T. S., Stork, P. J., and Cone, R. D. (1995) A colorimetric assay for measuring activation of Gs-and Gq coupled signaling pathways. Anal. Biochem. 226, 349–354.PubMedCrossRefGoogle Scholar
  168. 167.
    Gibson, S., Crosby, S. R., Stewart, M. F., Jennings, A. M., McCall, E., and White, A. (1994) Differential release of proopiomelanocortin-derived peptides from the human pituitary: evidence from a panel of two-site immunoradiometric assays. J. Clin. Endocrinol. Metab. 78, 835–841.PubMedCrossRefGoogle Scholar
  169. 168.
    Yogi, Y., Hashida, S., Ekman, R., Setoguchi, T., and Ishikawa, E. (1995) Noncompetitive enzyme immunoassay (hetero-two-site enzyme immunoassay) for y2 melanocyte-stimulating hormone (y2-MSH) and measurement of immunoreactive y2-MSH in plasma of healthy subjects. J. Clin. Lab. Anal. 9, 397–406.PubMedCrossRefGoogle Scholar
  170. 169.
    Siegrist, W., Oestreicher, M., Stutz, S., Girard, J., and Eberle, A. N. (1988). Radioreceptor assay for a-MSH using mouse B16 melanoma cells. J. Recept. Res. 8, 323–343.PubMedGoogle Scholar
  171. 170.
    Eberle, A. N., Jäggin Verin, V., Solca, F., Siegrist, W., Küenlin, C., Bagutti, C., Stutz, S., and Girard, J. (1988). Biologically active monoiodinated a-MSH derivatives for receptor binding studies using human melanoma cells. J. Recept. Res. 11, 311–322.Google Scholar
  172. 171.
    Buckley, D. I., Yamashiro, D., and Ramachandran, J. (1981) Synthesis of a corticotropin analog that retains full biological activity after iodination. Endocrinology 109, 5–9.PubMedCrossRefGoogle Scholar
  173. 172.
    Siegrist, W., Solca, F., Stutz, S., Giuffrè, L., Carrel, S., Girard, J., and Eberle, A. N. (1989) Characterization of receptors for a-melanocyte-stimulating hormone on human melanoma cells. Cancer Res. 49, 6352–6358.PubMedGoogle Scholar
  174. 173.
    Friedmann, P. S., Wren, F., Buffey, J., and MacNeil, S. (1990) a-MSH causes a small rise in cAMP but has no effect on basal or ultraviolett-stimulated melanogenesis in human melanocytes. Br. J. Dermatol. 123, 145–151.PubMedCrossRefGoogle Scholar
  175. 174.
    Siegrist, W., Drozdz, R., Cotti, R., Willard, D.H., Wilkison, W. O., and Eberle, A. N. (1997) Interaction of a-melanotropin and agouti on B16 melanoma cells: evidence for inverse agonism of agouti. J. Recept. Signal Transduct. Res. 17, 75–98.PubMedCrossRefGoogle Scholar
  176. 175.
    Buffey, J., Thody, A. J., Bleehen, S. S., and MacNeil, S. (1992) a-Melanocytestimulating hormone stimulates protein kinase C activity in murine B16 melanoma. J. Endocrinol. 133, 333–340.CrossRefGoogle Scholar
  177. 176.
    Siegrist, W., Sauter, P., and Eberle, A. N. (1995) A selective protein kinase C inhibitor (CGP 41251) positively and negatively modulates melanoma cell MSH receptors. J. Recept. Signal Transduct. Res. 15, 283–296.PubMedCrossRefGoogle Scholar
  178. 177.
    Reilein, A. R., Tint, I. S., Peunova, N. I., Enikolopov, G. N., and Gelfand, V. I. (1998) Regulation of organelle movement in melanophores by protein kinase A (PKA), protein kinase C (PKC), and protein phosphatase 2A (PP2A). J. Cell Biol. 142, 803–813.PubMedCrossRefGoogle Scholar
  179. 178.
    Park, H. Y., Russakovsky, V., Ao, Y., Fernandez, E., and Gilchrest, B. A. (1996) a-Melanocyte stimulating hormone-induced pigmentation is blocked by depletion of protein kinase C. Exp. Cell Res. 227, 70–79.Google Scholar
  180. 179.
    McLeod, S. D., Smith, C., and Mason, R. S. (1995) Stimulation of tyrosinase in human melanocytes by pro-opiomelanocortin-derived peptides. J. Endocrinol. 146, 439–447.PubMedCrossRefGoogle Scholar
  181. 180.
    Kapas, S., Purbrick, A., and Hinson, J. P. (1995) Role of tyrosine kinase and protein kinase C in the steroidogenic actions of angiotensin II, a-melanocyte-stimulating hormone and corticotropin in the rat adrenal cortex. Biochem. J. 305, 433–438.PubMedGoogle Scholar
  182. 181.
    Konda, Y., Gantz, I., DelValle, J. Shimoto, Y., Miwa, H., and Yamada, T. (1994) Interaction of dual intracellular signaling pathways activated by the melanocortin3 receptor. J. Biol. Chem. 269, 13162–13166.PubMedGoogle Scholar
  183. 182.
    De Graan, P. N. E., Eberle, A. N., and van de Veerdonk, F. C. G. (1982) Calcium sites in MSH stimulation of Xenopus melanophores: studies with photoreactive a-MSH. Cell. Mol. Endocrinol. 26, 327–339.CrossRefGoogle Scholar
  184. 183.
    Gerst, J. E., Sole, J., and Salomon, Y. (1987) Dual regulation of 3-melanotropin receptor function and adenylate cyclase by calcium and guanosine nucleotides in the M2R melanoma cell line. Mol. Pharmacol. 31, 81–88.PubMedGoogle Scholar
  185. 184.
    Kim, J. H., Kiefer, L. L., Woychik, R. P., Wilkison, W. O., Truesdale, A., Ittoop, O., Willard, D., Nichols, J., and Zemel, M. B. (1997) Agouti regulation of intracellular calcium: role of melanocortin receptors. Am. J. Physiol. 272, E379 - E384.PubMedGoogle Scholar
  186. 185.
    Castrucci, A. M., Hadley, M. E., Sawyer, T. K., Wilkes, B. C., al-Obeidi, F., Staples, D. J., de Vaux, A. E., Dym, O., Hintz, M. F., and Riehm, J. P. (1989) a-Melanotropin: the minimal active sequence in the lizard skin bioassay. Gen. Comp. Endocrinol. 73, 157–163.PubMedCrossRefGoogle Scholar
  187. 186.
    Miwa, H., Gantz, I., Konda, Y., Shimoto, Y., and Yamada, T. (1995) Structural determinants of the melanocortin peptides required for activation of melanocortin3 and melanocortin-4 receptors. J. Pharmacol. Exp. Ther. 273, 367–372.PubMedGoogle Scholar
  188. 187.
    Peng, P. J., Sahm, U. G., Doherty, R. V., Kinsman, R. G., Moss, S. H., and Pouton, C. W. (1997) Binding and biological activity of C-terminally modified melanocortin peptides: a comparison between their actions at rodent MC1 and MC3 receptors. Peptides 18, 1001–1008.PubMedCrossRefGoogle Scholar
  189. 188.
    Löw, M., Szalay, K. S., and Kisfaludy, L. (1990) Role of chain termini in selective steroidogenic effect of ACTH/MSH(4–10) on isolated adrenocortical cells. Peptides 11, 29–31.PubMedCrossRefGoogle Scholar
  190. 189.
    Sahm, U. G., Olivier, G. W., Branch, S. K., Moss, S. H., and Pouton, C. W. (1994) Synthesis and biological evaluation of a-MSH analogues substituted with alanine. Peptides 15, 1297–1302.PubMedCrossRefGoogle Scholar
  191. 190.
    Sawyer, T. K., Sanfilippo, P. J., Hruby, V. J., Engel, M. H., Heward, C. B., Burnett, J. B., and Hadley, M. E. (1980) 4-Norleucine, 7-D-phenylalanine-a-melanocytestimulating hormone: a highly potent a-melanotropin with ultralong biological activity. Proc. Natl. Acad. Sci. U.S.A. 77, 5754–5758.Google Scholar
  192. 191.
    Haskell-Luevano, C., Miwa, H., Dickinson, C., Hadley, M. E., Hruby, V. J., Yamada, T., and Gantz, I. (1996) Characterizations of the unusual dissociation properties of melanotropin peptides from the melanocortin receptor, hMC1-R. J. Med. Chem. 39, 432–435.PubMedCrossRefGoogle Scholar
  193. 192.
    Sawyer, T. K., Hruby, V. J., Darman, P. S., and Hadley, M. E. (1982) [half-Cys4, half-Cys10]-a-melanocyte-stimulating hormone: a cyclic a-melanotropin exhibiting superagonist biological activity. Proc. Natl. Acad. Sci. U.S.A. 79, 1751–1755.PubMedCrossRefGoogle Scholar
  194. 193.
    Sawyer, T. K., Staples, D. J., de Lauro Castrucci, A. M., and Hadley, M. E. (1989) Discovery and structure-activity relationships of novel a-melanocyte-stimulating hormone inhibitors. Peptide Res. 2, 140–146.Google Scholar
  195. 194.
    Sahm, U. G., Olivier, G. W., Branch, S. K., Moss, S. H. and Pouton, C. W. (1996) Receptor binding affinities and biological activities of linear and cyclic melanocortins in B16 murine melanoma cells expressing the native MC1 receptor. J. Pharm. Pharmacol. 48, 197–200.PubMedCrossRefGoogle Scholar
  196. 195.
    Haskell-Luevano, C., Shenderovich, M. D., Sharma, S. D., Nikiforovich, G. V., Hadley, M. E., and Hruby, V. J. (1995) Design, synthesis, biology, and conformations of bicyclic a-melanotropin analogues. J. Med. Chem. 38, 1736–1750.PubMedCrossRefGoogle Scholar
  197. 196.
    Sugg, E. E., Castrucci, A. M., Hadely, M. E., van Binst, G., and Hruby, V. J. (1988) Cyclic lactam analogues of Ac [N1e4]a-MSH411–NH2. Biochemistry 27, 8181–8188.PubMedCrossRefGoogle Scholar
  198. 197.
    Al-Obeidi, F., Castrucci, A. M., Hadley, M. E., and Hruby, V. J. (1989) Potent and prolonged acting cyclic lactam analogues of a-melanotropin: design based on molecular dynamics. J. Med. Chem. 32, 2555–2561.PubMedCrossRefGoogle Scholar
  199. 198.
    Dorr, R. T., Lines, R., Levine, N., Brooks, C., Xiang, L., Hruby, V. J., and Hadley, M. E. (1996) Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 58, 1777–1784.PubMedCrossRefGoogle Scholar
  200. 199.
    Al-Obeidi, F., Hruby, V. J., Yaghoubi, N., Marwan, M. M., and Hadley, M. E. (1992) Synthesis and biological activities of fatty acid conjugates of a cyclic lactam a-melanotropin. J. Med. Chem. 35, 118–123.PubMedCrossRefGoogle Scholar
  201. 200.
    Nikiforovich, G. V., Shenderovich, M. D., and Chipens, G. I. (1981) The space structure of a-melanotropin. FEBS Lett. 126, 180–182.PubMedCrossRefGoogle Scholar
  202. 201.
    Nikoforovich, G. V., Sharma, S.D., Hadley, M. E., and Hruby, V. J. (1998) Studies of conformational isomerism in a-melanocyte stimulating hormone by design of cyclic analogues. Biopolymers 46, 155–167.CrossRefGoogle Scholar
  203. 202.
    Lee, J. H., Lim, S. K., Huh, S. H., and Lee, W. (1998) Solution structures of the melanocyte-stimulating hormones by two-dimensional NMR spectroscopy and dynamical simulated-annealing calculations. Eur. J. Biochem. 257, 31–40.PubMedCrossRefGoogle Scholar
  204. 203.
    Yang, Y. K., Dickinson, C., Haskell-Luevano, C., and Gantz, I. (1997) Molecular basis for the interaction of [N1e4, D-Phe’]melanocyte stimulating hormone with the human melanocortin-1 receptor. J. Biol. Chem. 272, 23,000–23, 010.Google Scholar
  205. 204.
    Frandberg, P. A., Xu, X., and Chhajlani, V. (1997) Glutamine235 and arginine272in human melanocortin-5 receptor determines its low affinity to MSH. Biochem. Biophys. Res. Commun. 236, 489–492.PubMedCrossRefGoogle Scholar
  206. 205.
    Chhajlani, V., Xu, X., Blauw, J., and Sudarshi, S. (1996) Identification of ligand binding residues in extracellular loops of the melanocortin 1 receptor. Biochem. Biophys. Res. Commun. 219, 521–525.PubMedCrossRefGoogle Scholar
  207. 206.
    Haskell-Luevano, C., Hendrata, S., North, C., Sawyer, T. K., Hadley, M. E., Hruby, V. J., Dickinson, C., and Gantz, I. (1997) Discovery of prototype peptidomimetic agonists at the human melanocortin receptors MC 1-R and MC4-R. J. Med. Chem. 40, 2133–2139.PubMedCrossRefGoogle Scholar
  208. 207.
    Heizmann, G., Tanner, H., and Eberle, A. N. (1997) New ligands for the human melanoma MSH receptor identified by a peptoid library (oligo N-substituted glycines), In: Innovation and Perspectives in Solid-Phase Synthesis and Combinatorial Libraries 1996: Peptides, Proteins and Nucleic Acids, ( Epton, R. ed.) Mayflower Scientific, Birmingham. pp. 391–394.Google Scholar
  209. 208.
    Al-Obeidi, F., Hruby, V. J., Hadley, M. E., Sawyer, T. K., and Castrucci, A. M. (1990) Design, synthesis, and biological activities of a potent and selective a-melanotropin antagonist. Int. J. Pept Protein Res. 35, 228–234.PubMedCrossRefGoogle Scholar
  210. 209.
    Quillan, J. M. and Sadee, W. (1996) Structure-based search for peptide ligands that cross-react with melanocortin receptors. Pharm. Res. 13, 1624–1630.PubMedCrossRefGoogle Scholar
  211. 210.
    Hruby, V. J., Lu, D., Sharma, S. D., Castrucci, A. L., Kesterson, R. A., al-Obeidi, F. A., Hadley, M. E., and Cone, R. D. (1995) Cyclic lactam a-melanotropin analogues of Ac-N1e4-cyclo [Asps, D-Phe7, Lys] a-melanocyte-stimulating hormone-(4–10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors. J. Med. Chem. 38, 3454–3461.PubMedCrossRefGoogle Scholar
  212. 211.
    Schiöth, H. B., Muceniece, R., Mutulis, F., Prussis, P., Lindeberg, G., Sharma, S. D., Hruby, V. J., and Wikberg, J. E. (1997) Selectivity of cyclic [D-Nal’] and [DPhe’] substituted MSH analogues for the melanocortin receptor subtypes. Peptides 18, 1009–1013.PubMedCrossRefGoogle Scholar
  213. 212.
    Schiöth, H. B., Mutulis, F., Muceniece, R., Prusis, P., and Wikberg, J. E. (1998) Discovery of novel melanocortin-4 receptor selective MSH analogues. Br. J. Pharmacol. 124, 75–82.PubMedCrossRefGoogle Scholar
  214. 213.
    Kask, A., Rago, L., Mutulis, F., Pahkla, R., Wikberg, J. E., and Schöth, H. B. (1998) Selective antagonist for the melanocortin 4 receptor (HS014) increases food intake in free-feeding rats. Biochem. Biophys. Res. Commun. 245, 90–93.PubMedCrossRefGoogle Scholar
  215. 214.
    Kask, A., Mutulis, F., Muceniece, R., Pahkla, R., Mutule, I., Wikberg, J. E., Rago, L., and Schiöth, H. B. (1998) Discovery of a novel superpotent and selective melanocortin-4 receptor antagonist (HS024): evaluation in vitro and in vivo. Endocrinology 139, 5006–5014.PubMedCrossRefGoogle Scholar
  216. 215.
    Jayawickreme, C. K., Quillan, J. M., Graminski, G. F., and Lerner, M. R. (1994) Discovery and structure-function analysis of a-melanocyte-stimulating hormone antagonists. J. Biol. Chem. 269, 29,846–29, 854.Google Scholar
  217. 216.
    Siegrist, W., Willard, D. H., Wilkison, W. O., and Eberle, A. N. (1996) Agouti protein inhibits growth of B16 melanoma cells in vitro by acting through melanocortin receptors. Biochem. Biophys. Res. Commun. 218, 171–175.PubMedCrossRefGoogle Scholar
  218. 217.
    Siegrist, W., Drozdz, R., Cotti, R., Willard, D. H., Wilkison, W. O., and Eberle, A. N. (1997) Interactions of a-melanotropin and agouti on B16 melanoma cells: evidence for inverse agonism of agouti. J. Recept. Signal Transduct. Res. 17, 75–98.PubMedCrossRefGoogle Scholar
  219. 218.
    Don, R. T., Lines, R., Levine, N., Brooks, C., Xiang, L., Hruby, V. J., and Hadley, M. E. (1996) Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 58, 1777–1784.CrossRefGoogle Scholar
  220. 219.
    Wessels, H., Fuciarelli, K., Kansen, J., Hadley, M. E., Hruby, V. J., Dorr, R., and Levine, N. (1998) Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. J. Urol. 160, 389–393.CrossRefGoogle Scholar
  221. 220.
    Guarini, S., Bazzani, C., and Bertolini, A. (1997) Resuscitating effect of melanocortin peptides after prolonged respiratory arrest. Br. J. Pharmacol. 121, 1454–1460.PubMedCrossRefGoogle Scholar
  222. 221.
    Van de Meent, H., Hamers, F. P., Lankhorst, A. J., Joosten, E. A., and Gispen, W. H. (1997) Beneficial effects of the melanocortin a-melanocyte-stimulating hormone on clinical and neurophysiological recovery after experimental spinal cord injury. Neurosurgery 40, 122–130.PubMedGoogle Scholar
  223. 222.
    Salazar-Onfray, F., Nakazawa, T., Chhajlani, V., Perssson, M., Karre, K., Masucci, G., Celis, E., Sette, A., Southwood, S., Appella, E., and Kiessling, R. (1997) Synthetic peptides derived from the melanocyte-stimulating hormone receptor MC1-R can stimulate HLA-A2-restricted cytotoxic T lymphocytes that recognize naturally processed peptides on human melanoma cells. Cancer Res. 57, 4348–4355.PubMedGoogle Scholar
  224. 223.
    Murphy, J. R. (1988) Dipththeria-related peptide hormone gene fusions: a molecular genetic approach to chimeric toxin development. Cancer Treat. Res. 37, 123–140.PubMedCrossRefGoogle Scholar
  225. 224.
    Tatro, J. B., Wen, Z., Entwistle, M. L., Atkins, M. B., Smith, T. J., Reichlin, S., and Murphy, J. R. (1992) Interaction of an a-melanocyte-stimulating hormone-diphtheria toxin fusion protein with melanotropin receptors in human melanoma metastases. Cancer Res. 52, 2545–2548.PubMedGoogle Scholar
  226. 225.
    Ghanem, G. E., Libert, A., Arnould, R., Vercammen, A., and Lejeune, F. (1991) Human melanoma targeting with a-MSH-melphalan conjugate. Melanoma Res. 1, 105–114.PubMedCrossRefGoogle Scholar
  227. 226.
    Morandini, R., Süli-Vargha, H., Libert, A., Loir, B., Botyanszki, J. Medzihradszky, K., and Ghanem, G. (1994) Receptor-mediated cytotoxicity of a-MSH fragments containing melphalan in a human melanoma cell line. Int. J. Cancer 56, 129–133.PubMedCrossRefGoogle Scholar
  228. 227.
    Siegrist, W., Girard, J., and Eberle, A. N. (1991). Quantification of MSH receptors on mouse melanoma tissue by receptor autoradiography. J. Receptor Res. 11, 323–331.Google Scholar
  229. 228.
    Tatro, J. B., Atkins, M., Mier, J. W., Hardarson, S., Wolfe, H., Smith, T., Entwistle, M. L., and Reichlin, S. (1990). Melanotropin receptors demonstrated in situ in human melanoma. J. Clin. Invest. 85, 1825–1832.PubMedCrossRefGoogle Scholar
  230. 229.
    Garg, P. K., Alston, K. L., Welsh, P. C., and Zalutsky, M. R. (1996) Enhanced binding and inertness to dehalogenation of a-melanotropic peptides labeled using N-succinimidyl 3-iodobenzoate. Bioconjug. Chem. 7, 233–239.PubMedCrossRefGoogle Scholar
  231. 230.
    Bard, D. R., Wraight, E. P., and Knight, C. G. (1993) Bis-MSH-DTPA. A potential imaging agent for malignant melanoma. Ann. N.Y. Acad. Sci. 680, 451–453.PubMedCrossRefGoogle Scholar
  232. 231.
    Bagutti, C., Stolz, B., Albert, R., Bruns, C., Pless, J., and Eberle, A. N. (1993) [In]DTPA-labeled analogues of a-MSH for the detection of MSH receptors in vitro and in vivo. Ann. N.Y. Acad. Sci. 680, 445–447.PubMedCrossRefGoogle Scholar
  233. 232.
    Heppeler, A., Froidecaux, S., Mäcke, H. R., Jermann, E., Béhé, M., Powell, P., and Hennig, M. (1999) Radiometal labelled macrocyclic chelator derivatised somatostatin analogue with superb tumour targeting properties and potential for receptor mediated internal radiotherapy. Chem. Eur. J. 5, 1974–1981.CrossRefGoogle Scholar
  234. 233.
    Bard, D. R., Knight, C. G., and Page-Thomas, D. P. (1990) A chelating derivative of a-melanocyte stimulating hormone as a potential imaging agent for malignant melanoma. Br. J. Cancer 62, 919–922.PubMedCrossRefGoogle Scholar
  235. 234.
    Wraight, E. P., Bard, D. R., Maughan, T. S., Knight, C. G., and Page-Thomas, D. P. (1992) The use of a chelating derivative of a-melanocyte stimulating hormone for the clinical imaging of malignant melanoma. Br. J. Radiol. 65, 112–118.PubMedCrossRefGoogle Scholar
  236. 235.
    Bard, D. R. (1995) An improved imaging agent for malignant melanoma, based on [Nle4, D-Phe’]-a-melanocyte stimulating hormone. Nucl. Med. Commun. 16, 860–866.PubMedCrossRefGoogle Scholar
  237. 236.
    Bagutti, C., Stolz, B., Albert, R., Bruns, C., Pless, J., and Eberle, A. N. (1994) [1In]DTPA-labeled analogues of a-melanocyte-stimulating hormone for melanoma targeting: receptor binding in vitro and in vivo. Int. J. Cancer 58, 749–755.CrossRefGoogle Scholar
  238. 237.
    Vaidyanathan, G. and Zalutsky, M. R. (1997) Fluorine-18-labeled [Nle4, D-Phe’]a-MSH, an a-melanocyte stimulating hormone analogue. Nucl. Med. Biol. 24, 171–178.PubMedCrossRefGoogle Scholar
  239. 238.
    Giblin, M. F., Jurisson, S. S., and Quinn, T. P. (1997) Synthesis and characterization of rhenium-complexed a-melanotropin analogs. Bioconjug. Chem. 8, 347–353.PubMedCrossRefGoogle Scholar
  240. 239.
    Giblin, M. F., Wang, N., Hoffman, T. J., Jurisson, S. S., and Quinn, T. P. (1998) Design and characterization of a-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination. Proc. Natl. Acad. Sci. U.S.A. 95, 12814–12818.PubMedCrossRefGoogle Scholar
  241. 240.
    Eberle, A. N. (1993) Peptides containing multiple photolabels: a new tool for the analysis of ligand-receptor interactions: Reversible long-lasting stimulation and inhibition of MSH receptors by multiple photocrosslinks with a-MSH. J. Recept. Res. 13, 27–37.PubMedGoogle Scholar
  242. 241.
    Eberle, A. N. (1995) Transformation of an irreversible MSH antagonist into an irreversible MSH agonist by differential receptor crosslinking using the photo-affinity technique. J. Mol. Recognit. 8, 47–51.PubMedCrossRefGoogle Scholar
  243. 242.
    Siili-Vargha, H., Botyanszki, J., Medzihradszky-Schweiger, H., and Medzihradszky, K. (1990) Synthesis of a-MSH fragments containing phenylalanine mustard for receptor studies. Int. J. Pept. Protein Res. 36, 308–315.CrossRefGoogle Scholar
  244. 243.
    Solca, F. F., Salomon, Y., and Eberle, A. N. (1991) Heterogeneity of the MSH receptor among B16 murine melanoma subclones. J. Recept. Res. 11, 379–390.PubMedGoogle Scholar
  245. 244.
    Ahmed, A. R., Olivier, G. W., Adams, G., Erskine, M. E., Kinsman, R. G., Branch, S. K., Moss, S. H., Notarianni, L. J., and Pouten, C. W. (1992) Isolation and partial purification of a melanocyte-stimulating hormone receptor from B16 murine melanoma cells: a novel approach using a cleavable biotinylated photoactivated ligand and streptavidin-coated magnetic beads. Biochem. J. 286, 377–382.PubMedGoogle Scholar
  246. 245.
    Chakraborty, A. K., Orlow, S. J., Bolognia, J. L., and Pawelek, J. M. (1991) Structural/ functional relationships between internal and external MSH receptors: modulation of expression of Cloudman melanoma cells by UVB radiation. J. Cell. Physiol. 147, 1–6.PubMedCrossRefGoogle Scholar
  247. 246.
    Carrithers, M. D. and Lerner, M. R. (1996) Synthesis and characterization of bivalent peptide ligands targeted to G-protein-coupled receptors. Chem. Biol. 3, 537–542.PubMedCrossRefGoogle Scholar
  248. 247.
    Brandenburger, Y., Rose, K., Bagutti, C., and Eberle, A. N. (1999) Synthesis and receptor binding analysis of thirteen oligomeric a-MSH analogs. J. Recept. Signal Transduct. Res. 19, 467–480.PubMedCrossRefGoogle Scholar
  249. 248.
    Bagutti, C. and Eberle, A. N. (1993) Synthesis and biological properties of a biotinylated derivative of ACTH(1–17) for MSH receptor studies. J. Recept. Res. 13, 229–244.PubMedGoogle Scholar
  250. 249.
    Erskine-Grout, M. E., Olivier, G. W., Lucas, P., Sahm, U. G., Branch, S. K., Moss, S. H., Notarianni, L. J., and Pouton, C. W. (1996) Melanocortin probes for the melanoma MC 1 receptor: synthesis, receptor binding and biological activity. Melanoma Res. 6, 89–94.PubMedCrossRefGoogle Scholar
  251. 250.
    O’Hare, K. B., Duncan, R., Strohalm, J., Ulbrich, K., and Kopeckova, P. (1993) Polymeric drug-carrier containing doxorubicin and melanocyte-stimulating hormone: in vitro and in vivo evaluation against murine melanoma. J. Drug Target. 1, 217–229.PubMedCrossRefGoogle Scholar
  252. 251.
    Sharma, S. D., Granberry, M. E., Jiang, J., Leong, S. P., Hadley, M. E., and Hurby, V. J. (1994) Multivalent melanotropic peptide and fluorescent macromolecular conjugates: new reagents for characterization of melanotropin receptors. Bioconjug. Chem. 5, 591–601.PubMedCrossRefGoogle Scholar
  253. 252.
    Jiang, J., Sharma, S. D., Hruby, V. J., Bentley, D. L., Fink, J. L., and Hadley, M. E. (1996) Human epidermal melanocyte and keratinocyte melanocortin receptors: visualization by melanotropic peptide conjugated microspheres (latex beads). Pigment Cell Res. 9, 240–247.PubMedCrossRefGoogle Scholar
  254. 253.
    Jiang, J., Sharma, S. D., Fink, J. L., Hadley, M. E., and Hruby, V. J. (1996) Melanotropic peptide receptors: membrane markers of human melanoma cells. Exp. Dermatol. 5, 325–333.PubMedCrossRefGoogle Scholar
  255. 254.
    Chang, A. C. Y., Cochet, M., and Cohen, S. N. (1980) Structural organization of human genomic DNA encoding the pro-opiomelanocortin peptide. Proc. Natl. Acad. Sci. U.S.A. 77, 4890–4894.PubMedCrossRefGoogle Scholar
  256. 255.
    Chang, A. C. Y., Cochet, M., and Cohen, S. N. (1985) Structural analysis of the gene encoding human proopiomelanocortin: in Biogenetics of Neurohormonal Peptides. (Hâkanson, R. and Thorell, J. eds.), Academic Press, London, pp. 15–28.Google Scholar
  257. 256.
    Clark, A. J., Lavender, P. M., Besser, G. M., and Rees, L. H. (1989) Proopiomelanocortin mRNA size heterogeneity in ACTH-dependent Cushing’ s syndrome. J. Mol. Endocrinol. 2, 3–9.PubMedCrossRefGoogle Scholar
  258. 257.
    Crine, P., Lemieux, E., Fortin, S., Seidah, N. G., Lis, M., and Chrétien, M. (1981) Expression of variant forms of proopiomelanocortin, the common precursor to corticotropin and (3-lipotropin in the rat pars intermedia. Biochemistry 20, 2475–2481.PubMedCrossRefGoogle Scholar
  259. 258.
    Morris, J. C., Savva, D., and Lowry, P. J. (1995) Reduced expression of a naturally deleted form of human proopiomelanocortin complementary deoxyribonucleic acid after transfection into Chinese hamster ovary cells. Endocrinology 136, 195–201.PubMedCrossRefGoogle Scholar
  260. 259.
    Bicknell, A. B., Savva, D., and Lowry, P. J. (1996) Pro-opiomelanocortin and adrenal function. Endocr. Res. 22, 385–393.PubMedGoogle Scholar
  261. 260.
    Can, G., Abdel-Malek, Z., Porter-Gill, P. A., Gill, P., Boyce, S., Grabowski, G. A., Nordlund, J., and Farooqui, J. (1998) Identification and sequencing of a putative variant of proopiomelanocortin in human epidermis and epidermal cells in culture. J. Invest. Dermatol. 111, 485–491.PubMedCrossRefGoogle Scholar
  262. 261.
    Krude, H., Biebermann, H., Luck, W., Horn, R., Brabant, G., and Grüters, A. (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat. Genet. 19, 155–157.PubMedCrossRefGoogle Scholar
  263. 262.
    Hinney, A., Becker, I., Heibult, O., Nottebom, K., Schmidt, A., Ziegler, A., Mayer, H., Siegfried, W., Blum, W. F., Remschmidt, H., and Hebebrand, J. (1998) Systematic mutation screening of the pro-opiomelanocortin gene: identification of several genetic variants including three different insertions, one nonsense and two mis-sense point mutations in probands of different weight extremes. J. Clin. Endocrinol. Metab. 83, 3737–3741.PubMedCrossRefGoogle Scholar
  264. 263.
    Seidah, N. G., Day, R., Marcinkiewicz, M., and Chrétien, M. (1993) Mammalian paired basic amino acid convertases of prohormones and proproteins. Ann. N.Y. Acad. Sci. 680, 135–160.PubMedCrossRefGoogle Scholar
  265. 264.
    Marcinkiewicz, M., Day, R., Seidah, N. G., and Chrétien, M. (1993) Ontogeny of the prohormone convertases PC1 and PC2 in the mouse hypophysis and their colocalization with corticotropin and a-melanotropin. Proc. Natl. Acad. Sci. U.S.A. 90, 4922–4926.PubMedCrossRefGoogle Scholar
  266. 265.
    Tanaka, S., Yora, T., Nakayama, K., Inoue, K., and Kurosumi, K. (1997) Proteolytic processing of pro-opiomelanocortin occurs in acidifying secretory granules of AtT-20 cells. J. Histochem. Cytochem. 45, 425–436.PubMedCrossRefGoogle Scholar
  267. 266.
    Eipper, B. A., Bloomquist, B. T., Husten, E. J., Milgram, S. L., and Mains, R. E. (1993) Peptidylglycine a-amidating monooxygenase and other processing enzymes in the neurointermediate pituitary. Ann. N.Y. Acad. Sci. 680, 147–160.PubMedCrossRefGoogle Scholar
  268. 267.
    Dores, R. M., Steveson, T. C., and Price, M. L. (1993) A view of the N-acetylation of a-melanocyte-stimulating hormone and 13-endorphin from a phylogenetic perspective. Ann. N.Y. Acad. Sci. 680, 161–174.PubMedCrossRefGoogle Scholar
  269. 268.
    Castro, M. G. and Morrison, E. (1997) Post-translational processing of proopiomelanocortin in the pituitary and in the brain. Crit. Rev. Neurobiol. 11, 35–57.PubMedCrossRefGoogle Scholar
  270. 269.
    Rindler, M. J. (1998) Carboxypeptidase E, a peripheral membrane protein implicated in the targeting of hormones to secretory granules, co-aggregates with granule content proteins at acidic pH. J. Biol. Chem. 273, 31,180–31,185.CrossRefGoogle Scholar
  271. 270.
    Schmidt, W. K. and Moore, H. P. (1995) Ionic milieu controls the compartment-specific activation of pro-opiomelanocortin processing in AtT-20 cells. Mol. Biol. Cell 6, 1271–1285.PubMedGoogle Scholar
  272. 271.
    Kovacs, K., Horvath, E., Stefaneanu, L., Bilbao, J., Singer, W., Muller, P. J., Thapar, K., and Stone, E. (1997) Pituitary adenoma producing growth hormone and adrenocorticotropin: a histological, immunocytochemical, electron microscopic, and in situ hybridization study: case report. J. Neurosurg. 88, 1111–1115.Google Scholar
  273. 272.
    Dotman, C. H., Maia, A., Cruijsen, P. M. J. M., Jenks, B. G., and Roubos, E. W. (1998) Inhibitory and stimulatory control of proopiomelanocortin biosynthesis in the intermediate pituitary of Xenopus laevis. Ann. N.Y. Acad. Sci. 839, 472–474.CrossRefGoogle Scholar
  274. 273.
    Picon, A., Leblond-Francillard, M., Raffin-Sanson, M. L., Lenne, F., Bertagna, X., and Keyzer, Y. (1995) Functional analysis of the human pro-opiomelanocortin promoter in the small cell lung carcinoma line DMS-79. J. Mol. Endocrinol. 15, 187–194.PubMedCrossRefGoogle Scholar
  275. 274.
    Spencer, C. M. and Eberwine, J. (1999) Cytoplasmic proteins interact with a translational control element in the protein-coding region of proopiomelanocortin mRNA. DNA Cell Biol. 18, 39–49.PubMedCrossRefGoogle Scholar
  276. 275.
    Ottaviani, E., Capriglione, T., and Franceschi, C. (1995) Invertebrate and vertebrate immune cells express pro-opiomelanocortin (POMC) mRNA. Brain Behay. Immunol. 9, 1–8.CrossRefGoogle Scholar
  277. 276.
    Duvaux-Miret, O., Stefano, G. B., Smith, E. M., Dissous, C., and Capron, A. (1992) Immunosuppression in the definitive and intermediate hosts of the human parasite Schistosoma mansoni. Proc. Natl. Acad. Sci. U.S.A. 89, 778–781.CrossRefGoogle Scholar
  278. 277.
    Salzet, M., Salzet-Raveillon, B., Cocquerelle, C., Verget-Bocquet, M., Pryor, S. C., Rialas, C. M., Laurent, V., and Stefano, G. B. (1997) Leech immunocytes contain proopiomelanocortin: nitric oxide mediates hemolymph proopiomelanocortin processing. J. Immunol. 159, 5400–5411.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Alex N. Eberle

There are no affiliations available

Personalised recommendations