Abstract
α-Melanotropin (α-melanocyte stimulating hormone, α-MSH), Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2, is one of the first peptide hormones isolated from the pituitary gland. The biologic functions of α-MSH and structure-activity relationships of α-MSH analogues before 1993 have been extensively researched and reviewed (1–12). This hormone plays a well-known and principal role in pigmentation. Other effects ascribed to this hormone include:
-
1.
Regulation of the release of pituitary and peripheral hormones, such as somatostatin and corticotropin
-
2.
Sebotrophic effects, adrenal steroidogenesis, immune response, and cardiovascular and metabolic effects
-
3.
Important roles in the nervous system, particularly in the central nervous system (CNS)
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Tilders, F. J. H., Swaab, D. F., and van Wimersma Greidanus, T. B. (1977) Melanocyte stimulating hormone: control, chemistry and effects, in Frontiers Hormone Research, Volume 4 (T. B. van Wimersma Greidanus, ed.) S. Karger AG, Basel, New York.
Thody, A. J. (1980) The MSH Peptides. Academic Press, New York.
Hadley, M. E., Heward, C. B., Hruby, V. J., Sawyer, T. K., and Yang, Y. C. (1981) Biologic actions of melanocyte-stimulating hormone. Ciba Found. Symp. 81, 244–262.
Medzihradszky, K. (1982) The bio-organic chemistry of alpha-melanotropin. Med. Res. Rev. 2, 247–270.
Hruby, V. J., Mosberg, H. I., Sawyer, T. K., Knittel, J. J., Rockway, T. W., Ormberg, J., Darman, P., Chan, W. Y., and Hadley, M. E. (1983) Conformational and dynamic considerations in the design of peptide hormone analogs. Biopolymers 22, 517–530.
Hruby, V. J., Wilkes, B. C., Cody, W. L., Sawyer, T. K., and Hadley, M. E. (1984) Melanotropins: structural, conformational and biologic considerations in the development of superpotent and superprolonged analogs. Pept. Protein Rev. 3, 1–64.
Hadley, M. E. (1988) The Melanotropic Peptides. CRC Press, Boca Raton, FL.
Eberle, A. N. (1988) The Melanotropins. Chemistry, Physiology and Mechanisms of Action. S. Karger, Basel, Switzerland.
Castrucci, A. M. L., Sawyer, T. K., Al-Obeidi, F., Hruby, V. J., and Hadley, M. E. (1990) Melanotropic peptide antagonists: recent discoveries and biomedical implication. Drugs Future 15, 41–55.
Hruby, V. J., Sharma, S. D., Toth, K., Jaw, J. Y., Al-Obeidi, F., Sawyer, T. K., and Hadley, M. E. (1993) Design, synthesis, and conformation of superpotent and prolonged acting melanotropins. Ann. N. Y. Acad. Sci. 680, 51–63.
Scharrer, B., Smith, E. M., and Stefano, G. B. (1994) Neuropeptides and Immunoregulation. Springer-Verlag, New York.
Hadley, M. E. (1996) The melanotropic hormones, in Endocrinology, Prentice-Hall, Upper Saddle River, NJ, pp. 153–176.
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 257, 1248–1251.
Chhajlani, V. and Wikberg, J. E. (1992) Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA. FEBS Lett. 309, 417–420.
Chhajlani, V., Muceniece, R., and Wikberg, J. E. (1993) Molecular cloning of a novel human melanocortin receptor. Biochem. Biophys. Res. Commun. 195, 866–873. [published erratum appears in Biochem. Biophys. Res. Commun. 1996 Jan 17; 218: 638].
Cone, R. D., Mountjoy, K. G., Robbins, L. S., Nadeau, J. H., Johnson, K. R., RoselliRehfuss, L., and Mortrud, M. T. (1993) Cloning and functional characterization of a family of receptors for the melanotropic peptides. Ann. N.Y. Acad. Sci. 680, 342–363.
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.
Gantz, I., Miwa, H., Konda, Y., Shimoto, Y., Tashiro, T., Watson, S. J., Delvalle, J., and Yamada, T. (1993) Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J. Biol. Chem. 268, 15174–15179.
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.
Schioth, H. B., Chhajlani, V., Muceniece, R., Klusa, V., and Wikberg, J. E. (1996) Major pharmacological distinction of the ACTH receptor from other melanocortin receptors. Life Sci. 59, 797–801.
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-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biologic activity. Proc. Natl. Acad. Sci. U. S. A. 77, 5754–5758.
Sawyer, T. K., Hruby, V. J., Darman, P. S., and Hadley, M. E. (1982) [halfCys4,half-Cys10]-alpha-Melanocyte-stimulating hormone: a cyclic alphamelanotropin exhibiting superagonist biologic activity. Proc. Natl. Acad. Sci. U. S. A. 79, 1751–1755.
Nikiforovich, G. V., Rozenblit, S. A., Shenderovich, M. D., and Chipens, G. I. (1984) Possible bioactive conformations of alpha-melanotropin. FEBS Lett. 170, 315–320.
Al-Obeidi, F., Hadley, M. E., Pettitt, B. M., and Hruby, V. J. (1989) Design of a new class of superpotent a-melanotropins based on quenched dynamic simulations. J. Am. Chem. Soc. 111, 3413–3416.
Al-Obeidi, F., Castrucci, A. M. L., Hadley, M. E., and Hruby, V. J. (1989) Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics. J. Med. Chem. 32, 2555–2561.
Al-Obeidi, F., Hruby, V. J., Yaghoubi, N., Marwan, M. M., and Hadley, M. E. (1992) Synthesis and biologic activities of fatty acid conjugates of a cyclic lactam alpha-melanotropin. J. Med. Chem. 35, 118–123.
Hadley, M. E., Al-Obeidi, F., Hruby, V. J., Weinrach, J. C., Freedberg, D., Jiang, J. W., and Stover, R. S. (1991) Biologic activities of melanotropic peptide fatty acid conjugates. Pigment Cell Res. 4, 180–185.
Chaturvedi, D.N., Knittel, J. J., Hruby, V. J., Castrucci, A. M. L., and Hadley, M.E. (1984)Synthesis and biologic actions of highly potent and prolonged acting biotin-labeled melanotropins. J. Med. Chem. 27, 1406–1410.
Sugg, E. E., Cody, W. L., Abdel-Malek, Z., Hadley, M. E., and Hruby, V. J. (1986) D-Isomeric replacements within the 6–9 core sequence of Ac-[Nle4]-alpha-MSH4–11-NH,: a topological model for the solution conformation of alpha-melanotropin. Biopolymers 25, 2029–2042.
Hruby, V. J., Kazmierski, W., Pettitt, B. M., and Al-Obeidi, F. (1988) Conformational constraints in the design of receptor selective peptides: conformational analysis and molecular dynamics, in Molecular Biology of Brain and Endocrine Peptidergic Systems (M. Chretien, M. and McKerns, K. W. eds. ), Plenum, pp. 13–27.
Hruby, V. J., Lu, D., Sharma, S.D., Castrucci, A. M. L., Kesterson, R. A., Al-Obeidi F. A., Hadley, M. E., and Cone, R. D. (1995) Cyclic lactam alpha-melanotropin analogues of Ac-Nle4-cyclo[Asp5, D-Phe7,Lys10] alpha-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.
Haskell-Luevano, C., Nikiforovich, G., Sharma, S.D., Yang, Y.-Y., Dickinson, C., Hruby, V. J., and Gantz, I. (1997) Biologic and conformational examination of stereochemical modifications using the template melanotropin peptide, Ac-Nlec[Asp-His-Arg-Trp-Ala-Lys]-NH2, on human melanocortin receptors. J. Med. Chem. 40, 1738–1748.
Haskell-Luevano, C., Boteju, L. W., Miwa, H., Dickinson, C., Gantz, I., Yamada, T., Hadley, M. E., and Hruby, V. J. (1995) Topographical modification of melanotropin peptide analogues with beta-methyltryptophan isomers at position 9 leads to differential potencies and prolonged biologic activities. J. Med. Chem. 38, 4720–4729.
Sawyer, T. K., Staples, D. J., Castrucci, A. M. L., and Hadley, M. E. (1989) Discovery and structure-activity relationships of novel alpha-melanocyte-stimulating hormone inhibitors. Pept. Res. 2, 140–146.
Al-Obeidi, F., Hruby, V. J., Hadley, M. E., Sawyer, T. K., and Castrucci, A. M. L. (1990) Design, synthesis, and biologic activities of a potent and selective alphamelanotropin antagonist. Int. J. Pept. Protein Res. 35, 228–234.
Sawyer, T. K., Staples, D. J., Castrucci, A. M. L., Hadley, M. E., Al-Obeidi, F. A., Cody, W. L., and Hruby, V. J. (1990) Alpha-melanocyte stimulating hormone message and inhibitory sequences: comparative structure-activity studies on melanocytes. Peptides 11, 351–357.
McCormack, A. M., Carter, R. J., Thody, A. J., and Shuster, S. (1982) Des-acetyl MSH and gamma-MSH act as partial agonists to alpha-MSH on the Anolis melanophore. Peptides 3, 13–16.
Yajima, H. and Kubo, K. (1965) Studies on peptides. II. Synthesis and physiological properties of n-histidyl-D-phenylalanyl-D-arginyl-n-tryptophanylglycine, an optical antipode of an active fragment of a-melanocyte-stimulating hormone. J. Am. Chem. Soc. 87, 2039–2044.
Yajima, H., Kawasaki, K., Okada, Y., and Lande, S. (1965) Studies on peptides. V. Color-lightening action of histidylphenylalanylarginyl-5-methoxytryptamine on frog skin in vitro. Biochem. Biophys. Acta 107, 141–143.
Yajima, H. and Kawasaki, K. (1968) Studies on peptides. XVII. Synthesis of N-alpha-acetyl-seryl-tyrosyl-seryl-methionyl-glutamyl-histidyl-phenylalanyl-arginyl)-5-methoxy-tryptamine and its physiological properties on the frog melanocyte in vitro. Chem. Pharm. Bull. (Tokyo) 16, 1379–1382.
Castrucci, A. M. L., Sherbrooke, W. C., Sawyer, T. K., Staples, D. J., Tuma, M. C. B., and Hadley, M. E. (1994) Discovery of an alpha-melanotropin antagonist effective in vitro. Peptides 15, 627–632.
Castrucci, A. M. L., Hadley, M. E., Sawyer, T. K., Wilkes, B. C., Al-Obeidi, F., Staples, D. J., de Vaux, A. E., Dym, O., Hintz, M. F., Riehm, J. P., Rao, K. R., and Hruby, V. J. (1989) alpha-Melanotropin: the minimal active sequence in the lizard skin bioassay. Gen. Comp. Endocrinol. 73, 157–163.
Sawyer, T. K., Staples, D. J., Castrucci, A. M. L., Hadley, M. E., Al-Obeidi, F. A., Cody, W. L., and Hruby, V. J. (1990) alpha-Melanocyte stimulating hormone message and inhibitory sequences: comparative structure-activity studies on melanocytes. Peptides 11, 351–357.
Adan, R. A., Oosterom, J., Ludvigsdottir, G., Brakkee, J. H., Burbach, J. P., and Gispen, W.H. (1994) Identification of antagonists for melanocortin MC3, MC4 and MC5 receptors. Eur. J. Pharmacol. 269, 331–337.
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.
Jayawickreme, C. K., Quillan, J. M., Graminski, G. F., and Lerner, M. R. (1994) Discovery and structure-function analysis of alpha-melanocyte-stimulating hormone antagonists. J. Biol. Chem. 269, 29846–29854.
Haskell-Luevano, C., Miwa, H., Dickinson, C., Hruby, V. J., Yamada, T., and Gantz, I. (1994) Binding and cAMP studies of melanotropin peptides with the cloned human peripheral melanocortin receptor, hMC1-R. Biochem. Biophys. Res. Commun. 204, 1137–1142.
Schioth, H. B., Muceniece, R., Wikberg, J. E., and Chhajlani, V. (1995) Characterisation of melanocortin receptor subtypes by radioligand binding analysis. Eur. J. Pharmacol. 288, 311–317.
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, hMC 1-R. J. Med. Chem. 39, 432–435.
Schioth, H. B., Muceniece, R., and Wikberg, J. E. (1996) Characterisation of the melanocortin 4 receptor by radioligand binding. Pharmacol. Toxicol. 79, 161–165.
Adan, R. A., Cone, R. D., Burbach, J. P., and Gispen, W. H. (1994) Differential effects of melanocortin peptides on neural melanocortin receptors. Mol. Pharmacol. 46, 1182–1190.
Hadley, M. E., Anderson, B., Heward, C. B., Sawyer, T. K., and Hruby, V. J. (1981) Calcium-dependent prolonged effects on melanophores of [4-norleucine, 7-n-phenylalanine]-alpha-melanotropin. Science 213, 1025–1027.
Hadley, M. E., Hruby, V. J., Jiang, J., Sharma, S. D., Fink, J. L., Haskell-Luevano, C., Bentley, D. L., Al-Obeidi, F., and Sawyer, T. K. (1996) Melanocortin receptors: identification and characterization by melanotropic peptide agonists and antagonists. Pigment Cell Res. 9, 213–234.
Sharma, S. D., Jiang, J., Hadley, M. E., Bentley, D. L., and Hruby, V. J. (1996) Melanotropic peptide-conjugated beads for microscopic visualization and characterization of melanoma melanotropin receptors. Proc. Natl. Acad. Sci. U. S. A. 93, 13715–13720.
Li, S. J., Varga, K., Archer, P., Hruby, V. J., Sharma, S. D., Kesterson, R. A., Cone, R. D., and Kunos, G. (1996) Melanocortin antagonists define two distinct pathways of cardiovascular control by alpha-and gamma-melanocyte-stimulating hormones. J. Neurosci. 16, 5182–5188.
Schwyzer, R. (1977) ACTH: a short introductory review. Ann. N. Y. Acad. Sci. 297, 3–26.
Kastin, A. J., Zadina, J. E., Olson, R. D., and Banks, W. A. (1996) The history of neuropeptide research: version 5.a. Ann. N. Y. Acad. Sci. 780, 1–18.
Wessells, H., Fuciarelli, K., Hansen, J., Hadley, M. E., Hruby, V. J., Dorr, R., and Levine, N. (1998) Synthetic melanotropic peptide initiates erections in men with psycogenic erectile dysfunction: double-blind, placebo controlled crossover study. J. Urology 160, 389–393.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer Science+Business Media New York
About this chapter
Cite this chapter
Hruby, V.J., Han, G. (2000). The Molecular Pharmacology of Alpha-Melanocyte Stimulating Hormone. In: Cone, R.D. (eds) The Melanocortin Receptors. The Receptors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-031-5_8
Download citation
DOI: https://doi.org/10.1007/978-1-59259-031-5_8
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-082-3
Online ISBN: 978-1-59259-031-5
eBook Packages: Springer Book Archive