Skip to main content
SpringerLink
Log in

Melanocortin Receptor Expression and Function in the Nervous System

  • Chapter
The Melanocortin Receptors

Part of the book series: The Receptors ((REC))

Abstract

By the late 1970s, a range of evidence indicated that melanocortins could affect behavioral and visceral functions, neuroendocrine circuits, and the neurochemistry of the brain (1,2) in addition to well-characterized roles in pigmentation and adrenocortical steroidogenesis. The discovery of releasable neurosecretory pools of α-MSH in brain tissue (3), and the discovery of an intrinsic POMC (proopiomelanocortin) and melanocortin-containing neuron system in the brain (4,5), began to point to a potential role of endogenous central nervous system (CNS) melanocortins in regulating many of these functions. The facts that similar melanocortinergic systems exist in the brains of lower vertebrate species as primitive as the lungfish (6), and in mammals are predominantly distributed in the phylogenetically ancient visceral neuraxis, suggests that the melanocortin system may subserve highly conserved roles. As discussed below and in Chapters 4 and 13, a fairly extensive literature now supports a fundamental role of melanocortins in diverse CNS functions. Nevertheless, the identification of CNS-associated melanocortin receptors is a fairly recent development. Following the demonstration of MCR in the CNS in 1990 (7), the cloning of a family of MCR-encoding genes (see Chapter 7) paved the way for the recent explosive growth in interest in the physiological roles of melanocortins in the nervous system, and the molecular bases of melanocortin actions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. DeWied, D. and Jolies, J. (1982) Neuropeptides derived from pro—opiocortin: behavioral, physiological and neurochemical effects. Physiol. Rev. 62, 976–1059.

    CAS  Google Scholar 

  2. Dunn, A. J. (1984) Effects of ACTH, ß—lipotropin, and related peptides on the central nervous system, in: Peptides, Hormones, and Behavior ( Nemeroff, C. B. and Dunn, A. J., eds.), Spectrum, New York, pp. 273–347

    Chapter  Google Scholar 

  3. Warberg, J., Oliver, C., Eskay, R. L., Parker, C. R. J., Barnea, A., and Porter, J. C. (1977) Release of a—MSH from a synaptosome—enriched fraction prepaed from rat hypothalamic tissue. Front. Horm. Res. 4, 167–169.

    PubMed  CAS  Google Scholar 

  4. O’Donohue, T. L. and Dorsa, D. M. (1982) The opiomelanotropinergic neuronal and endocrine systems. Peptides 3, 353–395.

    Article  PubMed  Google Scholar 

  5. Gee, C. E., Chen, C.—L. C., Roberts, J. L., Thompson, R., and Watson, S. J. (1983) Identification of proopiomelanocortin neurones in rat hypothalamus by in situ hybridization. Nature 306, 374–376.

    Article  PubMed  CAS  Google Scholar 

  6. Vallarino, M., Tranchand Bunel, D., and Vaudry, H. (1993) Location and identification of a—melanocyte—stimulating hormone in the brain of the lungfish, Protopterus annectens. Ann. N. Y. Acad. Sci. 680, 634–637.

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Oilman, M. M., Wilson, B. D., Yang, Y.-K., Kerns, J. A., Chen, Y., Gantz, I., and Barsh, G. S. (1997) Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278, 135–138.

    Article  Google Scholar 

  9. Broberger, C., Johansen, J., Johansson, C., Schalling, M., and Hökfelt, T. (1998) The neuropeptide Y/agouti related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proc. Natl. Acad. Sci. USA 95, 15043–15048.

    Article  PubMed  CAS  Google Scholar 

  10. Yang, Y. K., Thompson, D. A., Dickinson, C. J., Wilken, J., Barsh, G. S., Kent, S. B., and Gantz, I. (1999) Characterization of Agouti-related protein binding to melanocortin receptors. Molecular Endocrinology 13, 148–155.

    Article  PubMed  CAS  Google Scholar 

  11. Pilcher, W. H. and Joseph, S. A. (1986) Differential sensitivity of hypothalamic and medullary opiocortin and tyrosine hydroxylase neurons to the neurotoxic effects of monosodium glutamate (MSG). Peptides 7, 783–789.

    Article  PubMed  CAS  Google Scholar 

  12. Emeson, R. B. and Eipper, B. A. (1986) Characterization of pro-ACTH/endorphin-derived peptides in rat hypothalamus. J. Neurosci. 6, 837–849.

    PubMed  CAS  Google Scholar 

  13. Mezey, E., Kiss, J. Z., Mueller, G. P., Eskay, R., O’ Donohue, T. L., and Palkovits, M. (1985) Distribution of the pro-opiomelanocortin derived peptides, adrenocorticotropic hormone, alpha-melanocyte-stimulating hormone and beta-endorphin (ACTH, a-MSH, VEND) in the rat hypothalamus. Brain Res. 328, 341–347.

    Article  PubMed  CAS  Google Scholar 

  14. Millington, W. R., Mueller, G. P., and O’Donohue, T. L. (1984) Regional heterogeneity in the ratio of a-MSH:(3-endorphin in the rat brain. Peptides 5, 841–843.

    Article  PubMed  CAS  Google Scholar 

  15. Nilaver, G., Zimmerman, E. A., Defendini, R., Liotta, A. S., Krieger, D. T., and Brownstein, M. J. (1979) Adrenocorticotropin and ß-lipotropin in the hypothalamus. J. Cell Biol. 81, 50–58.

    Article  PubMed  CAS  Google Scholar 

  16. Tsou, K., Khachaturian, H., Akil, H., and Watson, S. J. (1986) Immunocytochemical localization of pro-opiomelanocortin-derived peptides in the adult rat spinal cord. Brain Res. 378, 28–35.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    PubMed  CAS  Google Scholar 

  18. Wilson, B. D., Bagnol, D., Kaelin, C. B., Ollman, M. M., Gantz, I., Watson, S. J., and Barsh, G. S. (1999) Physiological and anatomical circuitry between Agouti-related protein and leptin signaling. Endocrinology 140, 2387–2397.

    Article  PubMed  CAS  Google Scholar 

  19. Haskell-Luevano, C., Chen, P., Li, C., Chang, K., Smith, M. S., Cameron, J. L., and Cone, R. D. (1999) Characterization of the neuroanatomical distribution of agouti-related protein immunoreactivity in the rhesus monkey and the rat. Endocrinology 140, 1408–1415.

    Article  PubMed  CAS  Google Scholar 

  20. Bagnol, D., Lu, X.-Y., Kaelin, C. B., Day, H. W., Ollman, O., Gantz, I., Akil, H., Barsh, G. S., and Watson, S. J. (1999) Anatomy of an endogenous antagonist: Relationship between agouti-related protein and proopiomelanocortin in brain. J. Neurosci.19, RC26.

    Google Scholar 

  21. Cannon, J. G., Tatro, J. B., Reichlin, S. R., and Dinarello, C. A. (1986) a-Melanocyte stimulating hormone inhibits immunostimulatory and inflammatory actions of interleukin-1. J. Immunol. 137, 2232–2236.

    Google Scholar 

  22. Lipton, J. M., Glyn, J. R., and Zimmer, J. A. (1981) ACTH and alpha-melanotropin in central temperature control. Fed. Proc. 40, 2760–2764.

    PubMed  CAS  Google Scholar 

  23. a. Tatro J. B. Endogenous antipyretics. Clin. Infect. Dis. (in press).

    Google Scholar 

  24. Catania, A. and Lipton, J. M. (1993) a-Melanocyte stimulating hormone in the modulation of host reactions. Endocr. Rev. 14, 564–576.

    Google Scholar 

  25. Tatro, J. B. and Entwistle, M. L. (1994) Distribution of melanocortin receptors in the lower brainstem of the rat. Ann. N.Y. Acad. Sci. 739, 311–314.

    Article  PubMed  CAS  Google Scholar 

  26. Tatro, J. B. (1993) Melanotropin receptors of the brain. Methods Neurosci. 11, 87–104.

    CAS  Google Scholar 

  27. Tatro, J. B. and Entwistle, M. L. (1994) Heterogeneity of brain melanocortin receptors suggested by differential ligand binding in situ. Brain Res. 635, 148–158.

    Article  CAS  Google Scholar 

  28. Sawyer, T. K., Sanfilippo, P. J., Hruby, V. J., Engel, M. H., Heward, C. B., Burnett, J. B., and Hadley, M. E. (1980) [N1e4,n-Phe’]a-melanocyte stimulating hormone: A highly potent a-melanotropin with ultralong biological activity. Proc. Natl. Acad. Sci. U. S. A. 77, 5754–5758.

    Google Scholar 

  29. Tatro, J. B. and Reichlin, S. (1987) Specific receptors for a-melanocyte-stimulating hormone are widely distributed in tissues of rodents. Endocrinology 121, 1900–1907.

    Article  PubMed  CAS  Google Scholar 

  30. 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.

    Article  PubMed  CAS  Google Scholar 

  31. Tatro, J. B., Entwistle, M. L., Lester, B. R., and Reichlin, S. (1990) Melanotropin receptors of murine melanoma characterized in cultured cells and demonstrated in experimental tumors in situ. Cancer Res. 50, 1237–1242.

    CAS  Google Scholar 

  32. Entwistle, M. L., Hann, L. E., Sullivan, D. A., and Tatro, J. B. (1990) Characterization of functional melanotropin receptors in lacrimal glands of the rat. Peptides 11, 477–483.

    Article  PubMed  CAS  Google Scholar 

  33. Chhajlani, V. and Wikberg, J. E. S. (1992) Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA. FEBS Lett. 309, 417–420.

    Article  PubMed  CAS  Google Scholar 

  34. Chhajlani, V., Muceniece, R., and Wikberg, J. E. S. (1993) Molecular cloning of a novel human melanocortin receptor. Biochem. Biophys. Res. Commun. 195, 866–873.

    Article  PubMed  CAS  Google Scholar 

  35. 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 POMC peptides in the medial basal hypothalamus and limbic system. Proc. Natl. Acad. Sci. U. S. A. 90, 8856–8860.

    Article  PubMed  CAS  Google Scholar 

  36. Desarnaud, F., Labbé, O., Eggerickx, D., Vassar, G., and Parmentier, M. (1994) Molecular cloning, functional expression and pharmacological characterization of a mouse melanocortin receptor gene. Biochem. J. 299, 367–373.

    PubMed  CAS  Google Scholar 

  37. Labbé, O., Desarnaud, F., Eggerickx, D., Vassart, G., and Parmentier, M. (1994) Molecular cloning of mouse melanocortin 5 receptor gene widely expressed in peripheral tissues. Biochemistry 33, 4543–4549.

    Article  PubMed  Google Scholar 

  38. Eberle, A. N. (1993) Peptides containing multiple photolabels: a new tool for the analysis of ligand-receptor interactions. J. Recept. Res. 13, 27–37.

    PubMed  CAS  Google Scholar 

  39. Bagutti, C. and Eberle, A. N. (1993) Synthesis and biological properties of a biotinylated derivative of ACTH1–17 for MSH receptor studies. J. Recept. Res. 13, 27–37.

    Google Scholar 

  40. Hadley, M. E., Hruby, V. J., Jiang, J., Sharma, S.D., Fink, J. L., Haskell-Leuvano, 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.

    Article  PubMed  CAS  Google Scholar 

  41. Erskine-Grout, M.-E., Olivier, G. W. J., Lucas, P., Sahm, U. G., Branch, S. K., Moss, S. H., Notarianni, L. J., and Pouton, C. W. (1996) Melanocortin probes for the melanoma MC1 receptor: synthesis, receptor binding and biological activity. Melanoma Res. 6, 89–94.

    Article  PubMed  CAS  Google Scholar 

  42. Van Houten, M., Khan, M. N., Walsh, R. J., Baquiran, G. B., Renaud, L. P., Bourque, C., Sgro, S., Gauthier, S., Chretien, M., and Posner, B. I. (1985) NHz terminal specificity and axonal localization of adrenocorticotropin binding sites in rat median eminince. Proc. Natl. Acad. Sci. U. S. A. 82, 1271–1275.

    Article  PubMed  Google Scholar 

  43. Tatro, J. B. (1993) Brain receptors for central and peripheral melanotropins. Ann. N. Y. Acad. Sci. 680, 621–625.

    Article  PubMed  CAS  Google Scholar 

  44. Herkenham, M. and Pert, C. B. (1982) Light microscopic localization of brain opiate receptors: a general autoradiographic method which preserves tissue quality. J. Neurosci. 28, 1129–1149.

    Google Scholar 

  45. Alvaro, J. D., Tatro, J. B., Quillan, J. M., Fogliano, M., Eisenhard, M., Lerner, M. R., Nestler, E. J., and Duman, R. S. (1996) Morphine down—regulates melanocortin-4 receptor expression in brain regions that mediate opiate addiction. Mol. Pharmacol. 50, 583–591.

    PubMed  CAS  Google Scholar 

  46. 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. Dey. Brain Res. 91, 93–110.

    Article  CAS  Google Scholar 

  47. Pranzatelli M. R. (1994) On the molecular mechanism of adrenocorticotrophic hormone in the CNS: neurotransmitters and receptors. Exper. Neurol. 125, 142–161.

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  49. Mousli, M., Bueb, J.-L., Bronner, C., Rouot, B., and Landry, Y. (1990) G protein activation: a receptor—independent mode of action for cationic amphiphilic neuropeptides and venom peptides. Trends Pharm. Sci. 11, 358–362.

    Article  PubMed  CAS  Google Scholar 

  50. Solca, F., Siegrist, W., Drodz, R., Girard, J., and Eberle, A. N. (1989) The receptor for a—melanotropin of mouse and human melanoma cells: Application of a potent photoaffinity label. J. Biol. Chem. 264, 14277–14281.

    PubMed  CAS  Google Scholar 

  51. Dyer, J. K., Ahmed, A. R. H., Oliver, G. W. J., Poulton, C. W., and Haynes, L. W. (1993) Solubilization partial characterization of the a—MSH receptor on primary rat Schwann cells. FEBS Lett 336, 103–106.

    Article  PubMed  CAS  Google Scholar 

  52. Solca, F. F., Chluba—de Tapia, J., Iwata, K., and Eberle, A. N. (1993) B16—G4F mouse melanoma cells: an MSH receptor—deficient cell clone. FEBS Lett. 322, 177–180.

    CAS  Google Scholar 

  53. Wong, G. and Pawelek, J. (1973) Control of phenotypic expression of cultured melanoma cells by melanocyte stimulating hormones. Nature New Biol. 241, 213–216.

    Article  PubMed  CAS  Google Scholar 

  54. Huang, Q.—H., Entwistle, M. L., Alvaro, J. D., Duman, R. S., Hruby, V. J., and Tatro, J. B. (1997) Antipyretic role of endogenous melanocortins mediated by central melanocortin receptors during endotoxin—induced fever. J. Neurosci. 17, 3343–3351.

    PubMed  CAS  Google Scholar 

  55. Adan, R. A. H., van der Kraan, M., Doorngos, R. P., Bar, P. R., Burbach, J. P. H., and Gispen, W. H. (1996) Melanocortin receptors mediate a—MSH—induced stimulation of neurite outgrowth in Neuro 2A cells. Mol. Brain Res. 36, 37–44.

    Article  PubMed  CAS  Google Scholar 

  56. Cholewinski, A. J. and Wilkin G. P. (1988) Astrocytes from forebrain, cerebellum, and spinal cord differ in their responses to vasoactive intestinal peptide. J. Neurochem. 51, 1626–1633.

    Article  PubMed  CAS  Google Scholar 

  57. 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 

  58. 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 

  59. Riedy, M. C., Timm, E. A. J., and Stewart, C. C. (1995) Quantitative RT-PCR for measuring gene expression. BioTechniques 18, 70–76.

    PubMed  CAS  Google Scholar 

  60. Emson, P. C. (1993) In-situ hybridization as a methodological tool for the neuroscientist. Trends Neurosci. 16, 9–16.

    Article  PubMed  CAS  Google Scholar 

  61. Griffon, N., Mignon, V., Facchinetti, P., Diaz, J., Schwartz, J., and Sokoloff, P. (1994) Molecular cloning and characterization of the rat fifth melancortin receptor. Biochem. Biophys. Res. Commun. 200, 1007–1014.

    Article  PubMed  CAS  Google Scholar 

  62. Vilaró, M. T., Palacios, J. M., and Mengod, G. (1995) Neurotransmitter receptor histochemistry: the contribution of in situ hybridization. Life Sci. 57, 1141–1154.

    Article  PubMed  Google Scholar 

  63. Désy, L. and Pelletier, G. (1978) Immunohistochemical localization of alphamelanocyte stimulating hormone (a-MSH) in the human hypothalamus. Brain Res. 154, 377–381.

    Article  PubMed  Google Scholar 

  64. Pilcher, W. H., Joseph, S. A., and McDonald, J. V. (1988) Immunocytochemical localization of pro-opiomelanocortin neurons in human brain areas subserving stimulation analgesia. J. Neurosurg. 68, 621–629.

    Article  PubMed  CAS  Google Scholar 

  65. Ibuki, T., Okamura, H., Miyazaki, M., Yanaihara, N., Zimmerman, E. A., and Ibata, Y. (1989) Comparative distribution of three opioid systems in the lower brainstem of the monkey (Macaca fuscata). J. Comp. Neurol. 279, 445–456.

    Article  PubMed  CAS  Google Scholar 

  66. Elias, C. F., Saper, C. B., Maratos-Flier, E., Tritos, N. A., Lee, C., Kelly, J., Tatro, J. B., Hoffman, G. E., Ollman, M. M., Barsh, G. S., Sakurai, T., Yanagisawa, M., and Elmquist, J. K. (1998) Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J. Comparative Neurol. 402, 442–459.

    Article  CAS  Google Scholar 

  67. Mihaly, E., Fekete, C., Liposits, Z., Stopa, E. G., and Lechan, R. M. (1999) Hypophysiotrophic thyrotropin-releasing hormone-synthesizing neurons of the human hypothalamus are innervated by axons containing neuropeptide Y and agouti-related protein. Soc. Neurosci. Abstr. 25, 1690.

    Google Scholar 

  68. Gantz, I., Kondaf, 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, 8248–8250.

    Google Scholar 

  69. 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.

    PubMed  CAS  Google Scholar 

  70. O’Donohue, T. L., Miller, R. L., and Jacobowitz, D. M. (1979) Identification, characterization and stereotaxic mapping of intraneuronal a-melanocyte stimulating hormone-like immunoreactive peptides in discrete regions of the rat brain. Brain Res. 176, 101–123.

    Article  PubMed  Google Scholar 

  71. Palkovits, M., Mezey, E., and Eskay, R. L. (1987) Pro-opiomelanocortin-derived peptides (ACTH/ß-endorphin/alpha-MSH) in brainstem baroreceptor areas of the rat. Brain Res. 436, 323–328.

    Article  PubMed  CAS  Google Scholar 

  72. Bronstein, D. M., Schafer, M. K. H., Watson, S. J., and Akil, H. (1992) Evidence that (3-endorphin is synthesized in cells in the nucleus tractus solitarius: detection of POMC mRNA. Brain Res. 587, 269–275.

    Article  PubMed  CAS  Google Scholar 

  73. Joseph, S. A. (1980) Immunoreactive adrenocorticotropin in rat brain: a neuroanatomical study using antiserum generated against synthetic ACTH1_39. Am. J. Anat. 158, 533–548.

    Article  PubMed  CAS  Google Scholar 

  74. Romagnano, M. A. and Joseph, S. A. (1983) Immunocytohemical localization of ACTH 1–39 in the brainstem of the rat. Brain Res. 276, 1–16.

    Article  PubMed  CAS  Google Scholar 

  75. Yamazoe, M., Shiosaka, S., Yagura, A., Kawai, Y., Shibasaki, T., Ling, N., and Tohyama, M. (1984) The distribution of a-melanocyte stimulating hormone (aMSH) in the central nervous system of the rat: An immunohistochemical study. II. Lower brain stem. Peptides 5, 721–727.

    Article  PubMed  CAS  Google Scholar 

  76. Tatro, J. B. and Entwistle, M. L. (1997) Distribution of melanocortin receptors in the rat spinal cord. Soc. Neurosci. Abstr. 23, 1492.

    Google Scholar 

  77. Klemcke, H. G. and Pond, W. G. (1990) Porcine adrenal adrenocorticotropic hormone receptors: characterization, changes during neonatal development, and response to a stressor. Endocrinology 128, 2476–2488.

    Article  Google Scholar 

  78. Mountjoy, K. G., Mortrud, M. T., Low, M. J., Simerly, R. B., and Cone, R. D. (1994) Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol. Endocrinol. 8, 1298–1308.

    Article  PubMed  CAS  Google Scholar 

  79. Lichtensteiger, W. and Monnet, F. (1979) Differential response of dopamine neurons to a-melanotropin and analogues in relation to their behavioral potency. Life Sci. 25, 2079–2087.

    Article  PubMed  CAS  Google Scholar 

  80. Schiöth, H. B., Muceniece, R., Wikberg, J. E. S., and Chhajlani, V. (1995) Characterisation of melanocortin receptor subtypes by radioligand binding analysis. Eur. J. Pharmacol. 288, 311–317.

    Article  PubMed  Google Scholar 

  81. Schiöth, H. B., Muceniece, R., and Wikberg, J. E. S. (1996) Characterisation of the melanocortin 4 receptor by radioligand binding. Pharmacol. Toxicol. 79, 161–165.

    Article  PubMed  Google Scholar 

  82. Mountjoy, K. G. and Wild, J. M. (1998) Melanocortin-4 receptor mRNA expression in the developing autonomic and central nervous systems. Brain Res. Del/. Brain Res. 107, 309–314.

    Article  CAS  Google Scholar 

  83. 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.

    Article  PubMed  CAS  Google Scholar 

  84. Van der Kraan, M., Adan, R. A. H., Entwistle, M. E., Gispen, W. H., Burbach, J. P. H., and Tatro, J. B. (1998) Expression of melanocortin 5 receptor in secretory epithelia supports a functional role in exocrine and endocrine glands. Endocrinology 139, 2348–2355.

    Article  PubMed  Google Scholar 

  85. Fathi, Z., Iben, L. G., and Parker, E. M. (1995) Cloning, expression, and tissue distribution of a fifth melanocortin receptor subtype. Neurochem. Res. 20, 107–113.

    Article  PubMed  CAS  Google Scholar 

  86. Cone, R. D., Mountjoy, K. G., Robbins, L. S., Nadeau, J. H., Johnson, K. R., Roselli-Rehfuss, 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.

    Article  PubMed  CAS  Google Scholar 

  87. Xia, Y., Wikberg, J. E. S., and Chhajlani, V. (1995) Expression of melanocortin 1 receptor in periaqueductal gray matter. NeuroReport 6, 2193–2196.

    Article  PubMed  CAS  Google Scholar 

  88. Rajora, N., Boccoli, G., Burns, D., Sharma, S., Catania, A. P., and Lipton, J. M. (1997) A-MSH modulates local and circulating tumor necrosis factor-a in experimental brain inflammation. J. Neurosci. 17, 2181–2186.

    PubMed  CAS  Google Scholar 

  89. 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 a-and y-melanocyte-stimulating hormones. J. Neurosci. 16, 5182–5188.

    PubMed  CAS  Google Scholar 

  90. Seeley, R. J., Yagaloff, K. A., Fisher, S. L., Burn, P., Thiele, T. E., van Dijk, G., Baskin, D. G., and Schwartz, M. W. (1997) Melanocortin receptors in leptin effects. Nature 390, 349.

    Article  PubMed  CAS  Google Scholar 

  91. 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., Burn, P., and Lee, F. (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131–141.

    Article  PubMed  CAS  Google Scholar 

  92. Yen, T. T., Gill, A. M., Frigeri, L. G., Barsh, G. S., and Wolff, G. L. (1994) Obesity, diabetes, and neoplasia in yellow AvY1- mice: ectopic expression of the agouti gene. FASEB J. 8, 479–488.

    PubMed  CAS  Google Scholar 

  93. Oilman, M. M., Wilson, B. D., Yang, Y.-K., Kerns, J. A., Chen, Y., Gantz, I., and Barsh, G. S. (1998) Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278, 135–138.

    Article  Google Scholar 

  94. Shiosaka, S., Shibasaki, T., and Tohyama, M. (1984) Bilateral a-melanocyte stimulating hormonergic fiber system from zona incerta to cerebral cortex: combined retrograde axonal transport and immunohistochemical study. Brain Res 309, 350–353.

    Article  PubMed  CAS  Google Scholar 

  95. Kohler, C. and Swanson, L. W. (1984) Acetylcholinesterase-containing cells in the lateral hypothalamic area are immunoreactive for a-melanocyte stimulating hormone and have cortical projections in te rat. Neurosci. Lett 49, 39–43.

    Article  PubMed  CAS  Google Scholar 

  96. Watson, S. J. and Akil, H. (1980) a-MSH in rat brain: occurrence within and outside of [3-endorphin neurons. Brain Res. 182, 217–223.

    Google Scholar 

  97. Khachaturian, H., Akil, H., Brownstein, M. J., Olney, J. W., Voigt, K. H., and Watson, S. J. (1986) Further characterization of the extra-arcuate alpha-melanocyte stimulating hormone-like material in hypothalamus: biochemical and anatomical studies. Neuropeptides 7, 291–313.

    Article  PubMed  CAS  Google Scholar 

  98. Nahon, J. L., Presse, F., Bittencourt, J. C., Sawchenko, P. E., and Vale W. (1990) The rat melanin-concentrating hormone messenger ribonucleic acid encodes multiple putative neuropeptides coexpressed in the dorsolateral hypothalamus. Endocrinology 125, 2056–2065.

    Article  Google Scholar 

  99. Oldfield, B. J. and McKinley, M. J. (1995) Circumventricular organs. in The Rat Nervous System, 2nd ed. ( Paxinos, G., ed.), Academic Press, New York, pp. 391–403.

    Google Scholar 

  100. Wilson, J. F. (1988) Low permeability of the blood-brain barrier to nanomolar concentrations of immunoreactive alpha-melanotropin. Psychopharmacology (Berl) 96, 262–266.

    Article  CAS  Google Scholar 

  101. Banks, W. A. and Kastin, A. J. (1995) Permeability of the blood-brain barrier to melanocortins. Peptides 16, 1157–1161.

    Article  PubMed  CAS  Google Scholar 

  102. Tatro, J. B. (1996) Receptor biology of the melanocortins, a family of neuroimmunomodulatory peptides. Neuroimmunomodulation 3, 259–284.

    Article  PubMed  CAS  Google Scholar 

  103. Jolles, J., Wiegant, V. M., and Gispen, W. H. (1978) Inhibition of behavioral effect of ACTH (1–24) and opioids by repeated administration. Neurosci. Lett 9, 261–266.

    Article  PubMed  CAS  Google Scholar 

  104. Xia, Y., and Wikberg, J. E. S. (1997) Postnatal expression of melanocortin-3 receptor in rat diencephalon and mesencephalon. Neuropharmacology 36, 217–224.

    Article  PubMed  CAS  Google Scholar 

  105. Khatchaturian, H., Lewis, M. E., Alessi, N. E., and Watson, S. J. (1985) Time of origin of opioid—containing neurons in the rat hypothalamus. J. Comp. Neurol. 236, 538–546.

    Article  Google Scholar 

  106. Kawai, Y., Shibasaki, T., Ling, N., and Tohyama, M. (1986) Ontogeny of y—melanocyte stimulating hormone in the brain and hypohysis of the rat: an immunohistochemical analysis. Dey. Brain Res. 28, 177–193.

    Article  CAS  Google Scholar 

  107. Alvaro, J. D., Tatro, J. B., and Duman, R. S. (1997) Melanocortins and opiate addiction. Life Sci. 61, 1–9.

    Article  PubMed  CAS  Google Scholar 

  108. Alvaro, J. D., Entwistle, M. L., Tatro, J. B., and Duman, R. S. (1996) Chronic cocaine administration increases melanocortin 4—receptor mRNA expression in rat striatum. Soc. Neurosci. Abstr. 22, 80.

    Google Scholar 

  109. Strand, F. L., Zuccarelli, L. A., Williams, K. A., Lee, S. J., Lee, T. S., Antonawich, F. J., and Alves, S. E. (1993) Melanotropins as growth factors. Ann. N. Y. Acad. Sci. 680, 29–50.

    Article  PubMed  CAS  Google Scholar 

  110. Hol, E. M., Gispen, W. H., and Bär, P. R. (1995) ACTH—related peptides: receptors and signal transduction systems involved in their neurotrophic and neuroprotective actions. Peptides 16, 979–993.

    Article  PubMed  CAS  Google Scholar 

  111. Mountjoy, K. G., Guan, J., Elia, C. J., Sirimanne, E. S., and Williams, C. E. (1999) Melanocortin-4 receptor messenger RNA expression is up-regulated in the non-damaged striatum following unilateral hypoxic-ischaemic brain injury. Neuroscience 89, 183–190.

    Article  PubMed  CAS  Google Scholar 

  112. Van der Kraan, M., Tatro, J. B., Entwistle, M. L., Brakkee, J. H., Burbach, J. P. H., Adan, R. A. H., and Gispen, W. H. (1999) Expression of melanocortin 4 receptors and pro-opiomelanocortin in the rat spinal cord in relation to neurotrophic effects of melanocortins. Mol. Brain Res. 63, 276–286.

    Google Scholar 

  113. Kiss, J. Z. and Williams, T. H. (1983) ACTH—immunoreactive boutons form synaptic contacts in the hypothalamic arcuate nucleus of rat: evidence for local opiocortin connections. Brain Res. 263, 142–146.

    Article  PubMed  CAS  Google Scholar 

  114. Lu, D., Willard, D., Patel, I. R., Kadwell, S., Overton, L., Kost, T., Luther, M., Chen, W., Woychik, R. P., Wilkison, W. O., and Cone, R. D. (1994) Agouti protein is an antagonist of the melanocyte—stimulating—hormone receptor. Nature 371, 799.

    Article  PubMed  CAS  Google Scholar 

  115. Shutter, J. R., Graham, M., Kinsey, A. C., Scully, S., Luthy, R., and Stark, K. L. (1997) Hypothalamic expression of ART, a novel gene related to agouti, is up—regulated in obese and diabetic mutant mice. Genes Dey. 11, 593–602.

    Article  CAS  Google Scholar 

  116. Cowley, M. A., Pronchuk, N., Fan, W., Dinulescu, D. M., Colmers, W. F., and Cone, R. D. (1999) Integration of NPY, AgRP, and melanocortin signals in the hypothalmic paraventricular nucleus: Evidence of a cellular basis for the adipostat. Neuron 24, 155–163.

    Article  PubMed  CAS  Google Scholar 

  117. Satoh, N., Ogawa, Y., Katsuura, G., Numata, Y., Masuzaki, H., Yoshimasa, Y., and Nakao, K. (1998) Satiety effect and sympathetic activation of leptin are mediated by hypothalamic melanocortin system. Neurosci. Lett. 249, 107–110.

    Article  PubMed  CAS  Google Scholar 

  118. Patterson, T. A., Hedde, J. R., She, L., Newsome, W. P., and Cornelius, P. (1999) Chronic infusion of a melanocortin agonist causes weight loss due to decreased food intake and increased metabolic rate. Soc. Neurosci. Abstr. 25, 618.

    Google Scholar 

  119. Elmquist, J. K., Elias, C. F., and Saper, C. B. (1999) From lesions to leptin: Hypothalamic control of food intake and body weight. Neuron 22, 221–232.

    Article  PubMed  CAS  Google Scholar 

  120. Elias, C. F., Lee, C., Kelly, J., Aschkenasi, C., Ahima, R. S., Couceyro, P. R., Kuhar, M. J., Saper, C. B., and Elmquist, J. K. (1998) Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron 21, 1375–1385.

    Article  PubMed  CAS  Google Scholar 

  121. Legradi, G. and Lechan, R. M. (1999) Agouti-related protein containing nerve terminals innervate thyrotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus. Endocrinol. 140, 3643–3652.

    Article  CAS  Google Scholar 

  122. Abou—Mohamed, G., Papapetropoulos, A., Ulrich, D., Catravas, J. D., Tuttle, R. R., and Caldwell, R. W. (1995) HP-228, a novel synthetic peptide, inhibits the induction of nitric oxide synthase in vivo but not in vitro. J. Pharmacol. Exp. Ther. 275, 584–591.

    Google Scholar 

  123. Corcos, I., Thompson, E. E., Omholt, P., Lee, M. D., McPherson, S., McDowell, R., Houghten, R., and Girten, B. (1997) HP-228 is a potent agonist of melanocortin receptor 4, and significantly attenuates obesity and diabetes in Zucker fatty rats. Soc. Neurosci. Abstr. 23, 673.

    Google Scholar 

  124. Hopkins, S. J. and Rothwell, N. J. (1995) Cytokines and the nervous system I: expression and recognition. Trends Neurosci. 18, 83–88.

    Article  PubMed  CAS  Google Scholar 

  125. Rothwell, N. J. and Hopkins, S. J. (1995) Cytokines and the nervous system II: actions and mechanisms of action. Trends Neurosci. 18, 130–136.

    Article  PubMed  CAS  Google Scholar 

  126. Patterson, P. H. (1995) Cytokines in Alzheimer’s disease and multiple sclerosis. Curr. Opin. Neurobiol. 5, 642–646.

    Article  PubMed  CAS  Google Scholar 

  127. 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—Nle4—cyclo[Asp5, D—Phe7, Lys10]— 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.

    Google Scholar 

  128. Tatro, J. B., Huszar, D., Fairchild-Huntress, V., and Huang, Q.-H. (1999) Role of the melanocortin-4 receptor in thermoregulatory responses to central IL1 p. Soc. Neurosci. Abstr. 25, 1558.

    Google Scholar 

  129. Huang, Q. H., Hruby, V. J., and Tatro, J. B. (1999) Role of central melanocortins in endotoxin-induced anorexia. Am. J. Physiol. 276, R864–71.

    PubMed  CAS  Google Scholar 

  130. Kobobun, K., O’Donohue, T. L., Handelman, G. E., Sawyer, T. K., Hruby, V. J., and Hadley, M. E. (1983) Behavioral effects of [4—norleucine, 7—D—phenylalanine]—a—melanocyte—stimulating hormone. Peptides 4, 721–724.

    Article  PubMed  CAS  Google Scholar 

  131. Kawai, Y., Inagaki, S., Shiosaka, S., Shibasaki, T., Ling, N., Tohyama, M., and Shiotani, Y. (1984) The distribution and projection of y—melanocyte stimulating hormone in the rat brain: an immunohistochemical analysis. Brain Res. 297, 21–32.

    Article  PubMed  CAS  Google Scholar 

  132. Swanson, L. W. (1992) Brain maps: Structure of the Rat Brain. Elsevier, New York.

    Google Scholar 

  133. Elmquist, J. K., Scammell, T. E., Jacobson, C. D., and Saper, C. B. (1996) Distribution of fos—like immunoreactivity in the rat brain following intravenous lipopolysaccharide administration. J. Comp. Neurol. 371, 85–103.

    Article  PubMed  CAS  Google Scholar 

  134. Uehara, Y., Shimizu, H., Sato, N., Tanaka, Y., Shimomura, Y., and Mori, M. (1992) Carboxy-terminal tripeptide of alpha-melanocyte-stimulating hormone antagonizes interleukin-1 induced anorexia. Eur. J. Pharmacol. 220, 119–122.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Jeffrey B. Tatro
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Vollum Institute, Oregon Health Sciences University, Portland, OR, USA

    Roger D. Cone

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Science+Business Media New York

About this chapter

Cite this chapter

Tatro, J.B. (2000). Melanocortin Receptor Expression and Function in the Nervous System. In: Cone, R.D. (eds) The Melanocortin Receptors. The Receptors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-031-5_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-031-5_6

  • 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

Publish with us

Policies and ethics

Search

Navigation