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Mechanism of action of melanocortin peptides

Possible role in astrocyte regulation

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Abstract

Melanocortin peptides exert pleiotropic effects in numerous cell types, controlling processes ranging from adrenal steroidogenesis and melanocyte pigmentation to lacrimation and nerve regeneration. The binding of melanocortins to specific cell surface receptors initiates cellular responses via GTP binding proteins (G-proteins). The affinity of these peptides to the receptor is modulated by extracellular Ca2+ ions, a property unique to melanocortin receptors. In astrocyte cultures derived from the rat brain, melanocortin stimulation elevates cAMP levels that appear to induce morphological changes. However, a transient proliferative response to melanocortins in these cells appears to be cAMP independent. The presence of melanocortin receptors in brain tissue and their unique Ca2+ dependence are discussed in relation to their putative role as regulators of astrocytes.

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References

  • Alessi N., Quinlan P., and Khachaturian H. (1988) MSG effects on beta-endorphin and alpha-MSH in the hypothalamus and caudal medulla.Peptides 9, 689–695.

    Article  PubMed  CAS  Google Scholar 

  • Ashkenazi A., Ramachandran J., and Capon D. J. (1989) Acetylcholine analogue stimulates DNA synthesis in brain-derived cells via specific muscarinic receptor subtypes.Nature 340, 146–150.

    Article  PubMed  CAS  Google Scholar 

  • Banker G. A. (1980) Trophic interactions between astroglial cells and hippocampal neurons in culture.Science 209, 809–810.

    Article  PubMed  CAS  Google Scholar 

  • Brenneman D. E., Nicol T., Warren D., and Bowers L. M. (1990) Vasoactive intestinal peptide: a neurotrophic releasing agent and an astroglial mitogen.J. Neurosci. Res. 25, 386–394.

    Article  PubMed  CAS  Google Scholar 

  • Cheitlin R., Buckley D.I., and Ramachandran J. (1985) The role of extracellular calcium in corticotropin steroidogenesis.J. Biol. Chem. 260, 5323–5327.

    PubMed  CAS  Google Scholar 

  • de Koning P. and Gispen W.H. (1988) A rationale for the use of melanocortins in the treatment of nervous tissues damage, inPharmacological Approaches to the Treatment of Brain and Spinal Cord Injuries, Stein D. G. and Sabel B., eds., Plenum, New York, pp. 233–258.

    Google Scholar 

  • de Wied D. and Ferrari W. (1986)Central Action of ACTH and Related Peptides. Spinger-Verlag, New York.

    Google Scholar 

  • de Wied D. and Jolles J. (1982) Neuropeptides derived from pro-opiocortin: behavioral, physiological, and neurochemical effects.Physiol. Rev. 62, 976–1059

    PubMed  Google Scholar 

  • Degani H., DeJordy J. O., and Salomon Y. (1991) Stimulation of cyclic AMP and phosphomonoester levels by melanotropin in melanoma cells:31P-NMR studies.Proc. Natl. Acad. Sci. USA 88, 1506–1510.

    Article  PubMed  CAS  Google Scholar 

  • Eberle A. N. (1988)The Melanotropins: Chemistry, Physiology and Mechanisms of Action. Karger, Basel, Switzerland.

    Google Scholar 

  • Eshel Y. and Salomon Y. (Unpublished Observations).

  • Evans T., McCarthy K. D., and Harden T. K. (1984) Regulation of cyclic AMP accumulation by peptide hormone receptors in immunocytochemically defined astroglial cells.J. Neurochem. 43, 131–138.

    Article  PubMed  CAS  Google Scholar 

  • Gasser U. E. and Hatten M. E. (1990) Neuron-glia interactions of rat hippocampal cellsin vitro: Glial guided neuronal migration and neuronal regulation of glial differentiation.J. Neurosci. 10, 1276–1285.

    PubMed  CAS  Google Scholar 

  • Gerst J. E. and Salomon Y. (1987) Inhibition by melittin and fluphenazine of melanotropin receptor function and adenylate cyclase in M2R melanoma cell membranes.Endocrinology 120, 1766–1772.

    Article  Google Scholar 

  • Gerst J. E. and Salomon Y. (1988) A synthetic analog of the calmodulin-binding domain of myosin light chain kinase inhibits melanotropin receptor function and activation of adenylate cyclase.J. Biol. Chem. 263, 7073–7078.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Gerst J. E., Sole J., Mather J. P., and Salomon Y. (1986) Regulation of adenylate cyclase by β-melanotropin in the M2R melanoma cell line.Mol. Cell. Endocrinol. 46, 137–147.

    Article  PubMed  CAS  Google Scholar 

  • Gerst J. E., Sole J., and Salomon Y. (1987) Dual regulation of β-melanotropin receptor function and adenylate cyclase by calcium and guanosine nucleotides in the melanoma cell line.Mol. Pharmacol. 31, 81–88.

    PubMed  CAS  Google Scholar 

  • Hanukoglu I., Feuchtwanger R., and Hanukoglu A. (1990) Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells.J. Biol. Chem. 265, 20,602–20,608.

    CAS  Google Scholar 

  • Hertz E., Fosmark H., Hertz L., Juurlink B. H., and Schousboe A. (1989)Preparation of primary cultures of mouse (rat) astrocytes. A dissection and tissue culture manual of the nervous system. Shahar A., De Vellis J., Vernadakis A., and Haber B., eds., Alan R. Liss, New York, pp. 105–109.

    Google Scholar 

  • Hertz L., Juurlink B. J., Fosmark H., and Schousboe A. (1982–83)Astrocytes in primary cultures. Neuroscience approached through cell culture. Pfeiffer S. M., ed., CRC Press, Boca Raton, FL, pp. 176–186.

    Google Scholar 

  • Hofmann K., Stehle C. J., and Finn F. M. (1988) Identification of a protein in adrenal particulates that binds adrenocorticotropin specifically and with high specificity.Endocrinology 123, 1355–1363.

    PubMed  CAS  Google Scholar 

  • Jahn R., Padel U., Porsch P., and Soling H. (1982) Adrenocorticotropic hormone and α-melanocyte-stimulating hormone induce secretion and protein phosphorylation in the rat lacrimal gland by activation of a cAMP-dependent pathway.Eur. J. Biochem. 126, 623–629.

    Article  PubMed  CAS  Google Scholar 

  • Johnston M. F., Kravitz E. A., Meiri H., and Rahamimoff, R. (1983). Adrenocorticotropic hormone causes long-lasting potentiation of transmitter release from frog motor nerve terminals.Science 220, 1071–1072.

    Article  PubMed  CAS  Google Scholar 

  • Kempski O., Wroblewska B., and Spatz M. (1987) Effects of forskolin on growth and morphology of cultured glial and cerebrovascular endothelial and smooth muscle cells.Int. J. Dev. Neurosci. 5, 435–445.

    Article  PubMed  CAS  Google Scholar 

  • Krieger D. T., Liotta A., and Brownstein M. J. (1977) Presence of corticotropin in brain of normal and hypophysectomized rats.Proc. Natl. Acad. Sci. USA 74, 645–649.

    Article  Google Scholar 

  • Leranth C., MacLusky J., and Naftolin F. (1986) Interconnections between neurotransmitter- and neuropeptide-containing neurons involved in gonadotropin release in the rat, inNeural and Endocrine Peptide Receptors. Moody T. W., ed., Plenum, New York, pp. 177–193.

    Google Scholar 

  • Lerner A. B. (1959) Mechanism of hormone action.Nature 184, 674–677.

    Article  PubMed  CAS  Google Scholar 

  • Li Z. G., Queen G., and LaBella F. S. (1990) Adrenocorticotropin, vasoactive intestinal peptide, growth hormone-releasing factor, and dynorphin compete for common receptors in brain and adrenal.Endocrinology 126, 1327–1333.

    PubMed  CAS  Google Scholar 

  • Lieba H., Garty N., Schmidt-Sole J., Pitterman 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.

    Article  Google Scholar 

  • Liotta A. S., Loudes C., McKelvy J. F., and Kreiger D. T. (1980) Biosynthesis of precursor corticotropin/endorphin-, corticotropin-, α-melanotropin-, β-lipotropin-, and β-endorphin-like material by cultured neonatal rat hypothalamic neurons.Proc. Natl. Acad. Sci. USA 77, 1880–1884.

    Article  PubMed  CAS  Google Scholar 

  • Londos C., Salomon Y., Lin M. C., Harwood J. P., Schramm M., Wolff J., and Rodbell M. (1974) 5′-Guanylyl imidodiphosphate, a potent activator of adenylate cyclase systems in eucaryotic cells.Proc. Natl. Acad. Sci. USA 71, 3087–3090.

    Article  PubMed  CAS  Google Scholar 

  • Mains R. E., Eipper B. A., and Ling N. (1977) Common precursor to corticotropins and endorphins.Proc. Natl. Acad. Sci. USA 74, 3014–3018.

    Article  PubMed  CAS  Google Scholar 

  • McCarthy K. D. and de Vellis J. (1980) Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue.J. Cell Biol. 85, 890–902.

    Article  PubMed  CAS  Google Scholar 

  • Meier E., Hertz L., and Schousboe A. (1991) Neurotransmitters as developmental signals.Neurochem. Int. 19, 1–15.

    Article  CAS  Google Scholar 

  • Nakanishi S., Inoue A., Kita T., Nakamura M., Chang A., Cohen S. N., and Numa S. (1979) Nucleotide sequence of cloned cDNA for bovine corticotropin-β-lipotropin precursor.Nature 278, 423–427.

    Article  PubMed  CAS  Google Scholar 

  • Orwoll E., Kendall J., Lamorena L., and McGilvra R. (1979) Adrenocorticotropin and melanocyte-stimulating hormone in the brain.Endocrinology 104, 1845–1852.

    PubMed  CAS  Google Scholar 

  • Pollenz R. S. and McCarthy K. D. (1986) Analysis of cyclic-AMP-dependent changes in intermediate filament protein phosphorylation and cell morphology in cultured astroglia.J. Neurochem. 47, 9–17.

    Article  PubMed  CAS  Google Scholar 

  • Ravid R., Swaab D. F., Van der Woude P. T., and Boer G. J. (1986) Immunocytochemically stained binding sites for oxytocin and α-melanocyte stimulating hormone in rat brain following ventricula administration.Brain Res. 379, 404–408.

    Article  PubMed  CAS  Google Scholar 

  • Roberts J. L. and Herbert E. (1977) Characterization of a common precursor to corticotropin and β-lipotropin: cell-free synthesis of the precursor and identification of corticotropin peptides in the molecule.Proc. Natl. Acad. Sci. USA 74, 4826–4830.

    Article  PubMed  CAS  Google Scholar 

  • Salomon Y. (1990) Melanocortin receptors: targets for control by extracellular calcium.Mol. Cell. Endocrinol. 70, 139–145.

    Article  PubMed  CAS  Google Scholar 

  • Scimonelli T. and Eberle A. N. (1987) Photoaffinity labelling of melanoma cell MSH receptors.FEBS Lett. 226, 134–138.

    Article  PubMed  CAS  Google Scholar 

  • Smith A. I. and Funder J. W. (1988) Proopiomelanocortin processing in the pituitary, central nervous system, and peripheral tissues.Endocrinol. Rev. 9, 159–179.

    Article  CAS  Google Scholar 

  • Smith E. M., Hughes T. K., Hashemi F., and Stefano G. B. (1992) Immunosuppressive effects of corticotropin and melanotropin and their possible significance in human immunodeficiency virus infection.Proc. Natl. Acad. Sci. USA 89, 782–786.

    Article  PubMed  CAS  Google Scholar 

  • Smith G. M., Rutishauser U., Silver J., and Miller R. H. (1990) Maturation of astrocytesin vitro alters the extent and molecular basis of neurite outgrowth.Dev. Biol. 138, 377–390.

    Article  PubMed  CAS  Google Scholar 

  • Solca F. F. A., Salomon Y., and Eberle A. N. (1991) Heterogeneity of the MSH receptor among B16 murine melanoma subclones.J. Recep. Res. 11, 379–390.

    CAS  Google Scholar 

  • Strand F. L., Rose K. J., Zuccarelli L. A., Kume J., Alves S., Antonawich F., and Garret L. Y. (1991) Neuropeptide hormones as neurotrophic factors.Physiol Rev. 71, 1017–1037.

    PubMed  CAS  Google Scholar 

  • Tanaka A., Pickering B. T., and Li C. H. (1962) Relationship of chemical structure to in vitro lipolytic activity of peptides occurring in adrenocorticotropic and melanocyte stimulating hormones.Arch. Biochem. Biophys. 99, 294–298.

    Article  PubMed  CAS  Google Scholar 

  • Tatro J. (1990) Melanotropin receptors in the brain are differentially distributed and recognize both corticotropin and α-melanocyte stimulating hormone.Brain Res. 536, 124–132.

    Article  PubMed  CAS  Google Scholar 

  • Thody A. J. (1980)The MSH Peptides. Academic Press, London, pp. 19–25.

    Google Scholar 

  • Van Calker D., Loffler F., and Hamprecht B. (1983) Corticotropin peptides and melanotropins elevate the level of adenosine 3′:5′-cyclic monophosphate in cultured murine brain cells.J. Neurochem. 40, 418–427.

    Article  PubMed  Google Scholar 

  • Watson S. J., Richard C. W., and Barchas J. D. (1978) Adrenocorticotropin in rat brain: immunocytochemical localization in cells and axons.Science 200, 1180–1182.

    Article  PubMed  CAS  Google Scholar 

  • Wolterink G. and Van Ree J. M. (1990) Functional recovery after destruction of dopamine systems in the nucleus accumbens of rats. III. Further analysis of the facilitating effect of the ACTH(4-9) analog ORG 2766.Brain Res. 507, 109–114.

    Article  PubMed  CAS  Google Scholar 

  • Wolterink G., Van Zanten E., Kamsteeg H., Radhakishun F. S., and Van Ree J. M. (1990a) Functional recovery after destruction of dopamine systems in the nucleus accumbens of rats. II. Facilitation by the ACTH(4-9) analog ORG 2766.Brain Res. 507, 101–108.

    Article  PubMed  CAS  Google Scholar 

  • Wolterink G., Van Zanten E., and Van Ree, J. M. (1990b) Functional recovery after destruction of dopamine systems in the nucleus accumbens of rats. IV. Delay by intra-accumbal treatment with ORG 2766- or α-MSH antiserum.Brain Res. 507, 115–120.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

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  1. The Department of Hormone Research, The Weizmann Institute of Science, 76100, Rehovot, Israel

    Muriel Zohar & Yoram Salomon

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  1. Muriel Zohar
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  2. Yoram Salomon
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Zohar, M., Salomon, Y. Mechanism of action of melanocortin peptides. J Mol Neurosci 4, 55–62 (1993). https://doi.org/10.1007/BF02736690

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