New ligands for melanocortin receptors

International Journal of Obesity

Volumn 32, Issue , 2008, Pages S19-S27

  Kaelin, C B ^a   Candille, S I ^a   Yu, B ^b   Jackson, P ^b   Thompson, D A ^b   Nix, M A ^b   Binkley, J ^a,c   Millhauser, G L ^b   Barsh, G S ^a  

^a STANFORD UNIVERSITY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Agouti; Agrp; G protein coupled receptors; Mahogany gene; Mc4r; MSH; defensins

Indexed keywords

AGOUTI PROTEIN; AGOUTI RELATED PROTEIN; ALPHA INTERMEDIN; BETA DEFENSIN; BETA DEFENSIN 1; BETA DEFENSIN 3; CORTICOTROPIN; G PROTEIN COUPLED RECEPTOR; LIGAND; MELANOCORTIN; MELANOCORTIN 1 RECEPTOR; MELANOCORTIN RECEPTOR; MELANOCORTIN RECEPTOR ANTAGONIST; NEUROPEPTIDE; PEPTIDE; RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ANTIINFLAMMATORY ACTIVITY; ANTIPYRETIC ACTIVITY; BRAIN REGION; CARBOXY TERMINAL SEQUENCE; DOG; ENERGY EXPENDITURE; FOOD INTAKE; GENOMICS; HOMEOSTASIS AND REGULATION; HUMAN; NEUROMODULATION; NONHUMAN; PHYSIOLOGICAL PROCESS; PIGMENTATION; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE; WEIGHT CONTROL; WEIGHT REDUCTION;

AGOUTI SIGNALING PROTEIN; AGOUTI-RELATED PROTEIN; ALPHA-MSH; ANIMALS; BETA-DEFENSINS; BODY WEIGHT; CENTRAL NERVOUS SYSTEM; DOGS; EATING; HOMEOSTASIS; HUMANS; LIGANDS; MELANOCORTINS; PIGMENTATION; RECEPTORS, MELANOCORTIN;

AGOUTI; CANIS FAMILIARIS; SWIETENIA; VERTEBRATA;

EID: 58149523595     PISSN: 03070565     EISSN: 14765497     Source Type: Journal    
DOI: 10.1038/ijo.2008.234     Document Type: Review

References (104)

1. Loos RJ, Bouchard C. FTO: the first gene contributing to common forms of human obesity. Obes Rev 2008; 9: 246–250.
2. Dina C. New insights into the genetics of body weight. Curr Opin Clin Nutr Metab Care 2008; 11: 378–384.
3. O’Rahilly S, Farooqi IS. Genetics of obesity. Philos Trans R Soc Lond B Biol Sci 2006; 361: 1095–1105.
4. Farooqi IS. Monogenic human obesity. Front Horm Res 2008; 36: 1–11.
5. Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW. Central nervous system control of food intake and body weight. Nature 2006; 443: 289–295.
6. Elmquist JK, Coppari R, Balthasar N, Ichinose M, Lowell BB. Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis. J Comp Neurol 2005; 493: 63–71.
7. Gao Q, Horvath TL. Neuronal control of energy homeostasis. FEBS Lett 2008; 582: 132–141.
8. Wikberg JE, Mutulis F. Targeting melanocortin receptors: an approach to treat weight disorders and sexual dysfunction. Nat Rev Drug Discov 2008; 7: 307–323.
9. Cone RD. Studies on the physiological functions of the melanocortin system. Endocr Rev 2006; 27: 736–749.
10. Voisey J, Carroll L, van Daal A. Melanocortins and their receptors and antagonists. Curr Drug Targets 2003; 4: 586–597.
11. Maaser C, Kannengiesser K, Kucharzik T. Role of the melanocortin system in inflammation. Ann N Y Acad Sci 2006; 1072: 123–134.
12. Slominski A, Tobin DJ, Shibahara S, Wortsman J. Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev 2004; 84: 1155–1228.
13. Lerner AB. The discovery of melanotropins. A history of pituitary endocrinology. Ann N Y Acad Sci 1993; 680: 1–12.
14. Strand FL. New vistas for melanocortins. Finally, an explanation for their pleiotropic functions. Ann N YAcad Sci 1999; 897: 1–16.
15. Gee CE, Chen CL, Roberts JL, Thompson R, Watson SJ. Identification of pro-opiomelanocortin neurones in rat hypothalamus by in situ cDNA–mRNA hybridization. Nature 1983; 306: 374–376.
16. Watson SJ, Richard III CW, Barchas JD. Adrenocorticotropin in rat brain: immunocytochemical localization in cells and axons. Science 1978; 200: 1180–1182.
17. Butler AA, Cone RD. Knockout studies defining different roles for melanocortin receptors in energy homeostasis. Ann N Y Acad Sci 2003; 994: 240–245.
18. Lubrano-Berthelier C, Dubern B, Lacorte JM, Picard F, Shapiro A, Zhang S et al. Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype–phenotype relationship, and lack of association with binge eating. J Clin Endocrinol Metab 2006; 91: 1811–1818.
19. Slominski A, Plonka PM, Pisarchik A, Smart JL, Tolle V, Wortsman J et al. Preservation of eumelanin hair pigmentation in pro-opiomelanocortin-deficient mice on a nonagouti (a/a) genetic background. Endocrinology 2005; 146: 1245–1253.
20. Yaswen L, Diehl N, Brennan MB, Hochgeschwender U. Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med 1999; 5: 1066–1070.
21. Wortley KE, Anderson KD, Yasenchak J, Murphy A, Valenzuela D, Diano S et al. Agouti-related protein-deficient mice display an age-related lean phenotype. Cell Metab 2005; 2: 421–427.
22. Kerns JA, Cargill EJ, Clark LA, Candille SI, Berryere TG, Olivier M et al. Linkage and segregation analysis of black and brindle coat color in domestic dogs. Genetics 2007; 176: 1679–1689.
23. Candille SI, Kaelin CB, Cattanach BM, Yu B, Thompson DA, Nix MA et al. A b-defensin mutation causes black coat color in domestic dogs. Science 2007; 318: 1418–1423.
24. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 2003; 3: 710–720.
25. Semple CA, Gautier P, Taylor K, Dorin JR. The changing of the guard: molecular diversity and rapid evolution of beta-defensins. Mol Divers 2006; 10: 575–584.
26. Dorin JR, Jackson IJ. Genetics. Beta-defensin repertoire expands. Science 2007; 318: 1395.
27. Lee TH, Lerner AB. Isolation of melanocyte-stimulating hormone from hog pituitary gland. J Biol Chem 1956; 221: 943–959.
28. Li CH, Geschwind II, Levy AL, Harris JI, Dixon JS, Pon NG et al. Isolation and properties of alpha-corticotrophin from sheep pituitary glands. Nature 1954; 173: 251–253.
29. Eipper BA, Mains RE. Structure and biosynthesis of proadrenocorticotropin/endorphin and related peptides. Endocr Rev 1980; 1: 1–27.
30. Mains RE, Eipper BA, Ling N. Common precursor to corticotropins and endorphins. Proc Natl Acad Sci USA 1977; 74: 3014–3018.
31. Rubinstein M, Stein S, Udenfriend S. Characterization of proopiocortin, a precursor to opioid peptides and corticotropin. Proc Natl Acad Sci USA 1978; 75: 669–671.
32. Nozaki M, Shimotani T, Uchida K. Gonadotropin-like and adrenocorticotropin-like cells in the pituitary gland of hagfish, Paramyxine atami; immunohistochemistry in combination with lectin histochemistry. Cell Tissue Res 2007; 328: 563–572.
33. Nozaki M, Takahashi A, Amemiya Y, Kawauchi H, Sower SA. Distribution of lamprey adrenocorticotropin and melanotropins in the pituitary of the adult sea lamprey, Petromyzon marinus. Gen Comp Endocrinol 1995; 98: 147–156.
34. Haitina T, Klovins J, Takahashi A, Lowgren M, Ringholm A, Enberg J et al. Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes. BMC Evol Biol 2007; 7: 101.
35. Stefano GB, Salzet-Raveillon B, Salzet M. Mytilus edulis hemolymph contains pro-opiomelanocortin: LPS and morphine stimulate differential processing. Brain Res Mol Brain Res 1999; 63: 340–350.
36. Salzet M, Salzet-Raveillon B, Cocquerelle C, Verger-Bocquet M, Pryor SC, Rialas CM et al. Leech immunocytes contain proopiomelanocortin: nitric oxide mediates hemolymph proopiomelanocortin processing. J Immunol 1997; 159: 5400–5411.
37. Stefano GB, Salzet M. Invertebrate opioid precursors: evolutionary conservation and the significance of enzymatic processing. Int Rev Cytol 1999; 187: 261–286.
38. Takahashi A, Kawauchi H. Evolution of melanocortin systems in fish. Gen Comp Endocrinol 2006; 148: 85–94.
39. Kawauchi H, Sower SA. The dawn and evolution of hormones in the adenohypophysis. Gen Comp Endocrinol 2006; 148: 3–14.
40. Campbell RK, Satoh N, Degnan BM. Piecing together evolution of the vertebrate endocrine system. Trends Genet 2004; 20: 359–366.
41. Kozak K, Costantino D, Lecaude S, Sollars C, Danielson P, Dores RM. Analyzing the radiation of the melanocortins in amphibians: cloning of POMC cDNAs from the pituitary of the urodele amphibians, Amphiuma means and Necturus maculosus. Peptides 2005; 26: 1920–1928.
42. Dores RM, Lecaude S, Bauer D, Danielson PB. Analyzing the evolution of the opioid/orphanin gene family. Mass Spectrom Rev 2002; 21: 220–243.
43. Danielson PB, Dores RM. Molecular evolution of the opioid/orphanin gene family. Gen Comp Endocrinol 1999; 113: 169–186.
44. Klovins J, Schioth HB. Agouti-related proteins (AGRPs) and agouti-signaling peptide (ASIP) in fish and chicken. Ann N Y Acad Sci 2005; 1040: 363–367.
45. Metz JR, Peters JJ, Flik G. Molecular biology and physiology of the melanocortin system in fish: a review. Gen Comp Endocrinol 2006; 148: 150–162.
46. Cerda-Reverter JM, Schioth HB, Peter RE. The central melanocortin system regulates food intake in goldfish. Regul Pept 2003; 115: 101–113.
47. Song Y, Cone RD. Creation of a genetic model of obesity in a teleost. FASEB J 2007; 21: 2042–2049.
48. Song Y, Golling G, Thacker TL, Cone RD. Agouti-related protein (AGRP) is conserved and regulated by metabolic state in the zebrafish, Danio rerio. Endocrine 2003; 22: 257–265.
49. Klovins J, Haitina T, Fridmanis D, Kilianova Z, Kapa I, Fredriksson R et al. The melanocortin system in Fugu: determination of POMC/AGRP/MCR gene repertoire and synteny, as well as pharmacology and anatomical distribution of the MCRs. Mol Biol Evol 2004; 21: 563–579.
50. McNulty JC, Jackson PJ, Thompson DA, Chai B, Gantz I, Barsh GS et al. Structures of the agouti signaling protein. J Mol Biol 2005; 346: 1059–1070.
51. McNulty JC, Thompson DA, Bolin KA, Wilken J, Barsh GS, Millhauser GL. High-resolution NMR structure of the chemically- synthesized melanocortin receptor binding domain AGRP (87–132) of the agouti-related protein. Biochemistry 2001; 40: 15520–15527.
52. Norton RS, Pallaghy PK. The cystine knot structure of ion channel toxins and related polypeptides. Toxicon 1998; 36: 1573–1583.
53. Hughes AL. Evolutionary diversification of the mammalian defensins. Cell Mol Life Sci 1999; 56: 94–103.
54. Patil AA, Cai Y, Sang Y, Blecha F, Zhang G. Cross-species analysis of the mammalian beta-defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract. Physiol Genomics 2005; 23: 5–17.
55. Zou J, Mercier C, Koussounadis A, Secombes C. Discovery of multiple beta-defensin like homologues in teleost fish. Mol Immunol 2007; 44: 638–647.
56. Castle WE, Little CC. On a modified Mendelian ratio among yellow mice. Science 1910; 32: 868–870.
57. Siracusa LD. The agouti gene: turned on to yellow. Trends Genet 1994; 10: 423–428.
58. Duhl DM, Vrieling H, Miller KA, Wolff GL, Barsh GS. Neomorphic agouti mutations in obese yellow mice. Nat Genet 1994; 8: 59–65.
59. Miller MW, Duhl DMJ, Vrieling H, Cordes SP, Ollmann MM, Winkes BM et al. Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the Lethal–Yellow mutation. Genes Dev 1993; 7: 454–467.
60. Bultman SJ, Michaud EJ, Woychik RP. Molecular characterization of the mouse agouti locus. Cell 1992; 71: 1195–1204.
61. Michaud EJ, Bultman SJ, Klebig ML, van Vugt MJ, Stubbs LJ, Russell LB et al. A molecular model for the genetic and phenotypic characteristics of the mouse lethal yellow (Ay) mutation. Proc Natl Acad Sci USA 1994; 91: 2562–2566.
62. Silvers WK. The agouti and extension series of alleles, umbrous and sable. In: The Coat Colors of Mice. Springer-Verlag: New York, 1979, pp 6–44.
63. Robbins LS, Nadeau JH, Johnson KR, Kelly MA, Roselli-Rehfuss L, Baack E et al. Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function. Cell 1993; 72: 827–834.
64. Yang YK, Ollmann MM, Wilson BD, Dickinson C, Yamada T, Barsh GS et al. Effects of recombinant agouti-signaling protein on melanocortin action. Mol Endocrinol 1997; 11: 274–280.
65. Ollmann MM, Lamoreux ML, Wilson BD, Barsh GS. Interaction of agouti protein with the melanocortin 1 receptor in vitro and in vivo. Genes Dev 1998; 12: 316–330.
66. Lu DS, Willard D, Patel IR, Kadwell S, Overton L, Kost T et al. Agouti protein is an antagonist of the melanocyte-stimulatinghormone receptor. Nature 1994; 371: 799–802.
67. Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 1997; 278: 135–138.
68. Yang YK, Thompson DA, Dickinson CJ, Wilken J, Barsh GS, Kent SB et al. Characterization of agouti-related protein binding to melanocortin receptors. Mol Endocrinol 1999; 13: 148–155.
69. Graham M, Shutter JR, Sarmiento U, Sarosi I, Stark KL. Overexpression of Agrt leads to obesity in transgenic mice. Nat Genet 1997; 17: 273–274.
70. Siegrist W, Drozdz R, Cotti R, Willard DH, Wilkison WO, Eberle AN. Interactions of alpha-melanotropin and agouti on B16 melanoma cells: Evidence for inverse agonism of agouti. J Recept Signal Transduct Res 1997; 17: 75–98.
71. Nijenhuis WA, Oosterom J, Adan RA. AgRP(83–132) acts as an inverse agonist on the human-melanocortin-4 receptor. Mol Endocrinol 2001; 15: 164–171.
72. Chai BX, Neubig RR, Millhauser GL, Thompson DA, Jackson PJ, Barsh GS et al. Inverse agonist activity of agouti and agoutirelated protein. Peptides 2003; 24: 603–609.
73. Jackson PJ, Douglas NR, Chai B, Binkley J, Sidow A, Barsh GS et al. Structural and molecular evolutionary analysis of Agouti and Agouti-related proteins. Chem Biol 2006; 13: 1297–1305.
74. Kiefer LL, Ittoop ORR, Bunce K, Truesdale AT, Willard DH, Nichols JS et al. Mutations in the carboxyl terminus of the agouti protein decrease agouti inhibition of ligand binding to the melanocortin receptors. Biochemistry 1997; 36: 2084–2090.
75. Kiefer LL, Veal JM, Mountjoy KG, Wilkison WO. Melanocortin receptor binding determinants in the agouti protein. Biochemistry 1998; 37: 991–997.
76. Gunn TM, Miller KA, He L, Hyman RW, Davis RW, Azarani A et al. The mouse mahogany locus encodes a transmembrane form of human attractin. Nature 1999; 398: 152–156.
77. He L, Gunn TM, Bouley DM, Lu XY, Watson SJ, Schlossman SF et al. A biochemical function for attractin in agouti-induced pigmentation and obesity. Nat Genet 2001; 27: 40–47.
78. Creemers JW, Pritchard LE, Gyte A, Le Rouzic P, Meulemans S, Wardlaw SL et al. Agouti-related protein is posttranslationally cleaved by proprotein convertase 1 to generate agouti-related protein (AGRP)83-132: Interaction between AGRP83-132 and melanocortin receptors cannot be influenced by syndecan-3. Endocrinology 2006; 147: 1621–1631.
79. Pritchard LE, White A. Agouti-related protein: more than a melanocortin-4 receptor antagonist? Peptides 2005; 26: 1759–1770.
80. Perry WL, Nakamura T, Swing DA, Secrest L, Eagleson B, Hustad CM et al. Coupled site-directed mutagenesis/transgenesis identifies important functional domains of the mouse agouti protein. Genetics 1996; 144: 255–264.
81. He L, Eldridge AG, Jackson PK, Gunn TM, Barsh GS. Accessory proteins for melanocortin signaling: attractin and mahogunin. Ann N Y Acad Sci 2003; 994: 288–298.
82. Ollmann MM, Barsh GS. Down-regulation of melanocortin receptor signaling mediated by the amino terminus of Agouti protein in Xenopus melanophores. J Biol Chem 1999; 274: 15837–15846.
83. Wright S. Color inheritance in mammals. J Hered 1917; 8: 224–235.
84. Wright S. Color inheritance in mammals-II. The mouse. J Hered 1917; 8: 373–378.
85. Searle AG. Comparative Genetics of Coat Color in Mammals. Academic Press: New York, NY, 1968.
86. Little CC. The Inheritance of Coat Color in Dogs. Comstock: Ithaca, NY, 1957.
87. Kerns JA, Newton J, Berryere TG, Rubin EM, Cheng JF, Schmutz SM et al. Characterization of the dog Agouti gene and a nonagouti mutation in German shepherd dogs. Mamm Genome 2004; 15: 798–808.
88. Kerns JA, Olivier M, Lust G, Barsh GS. Exclusion of melanocortin-receptor (mc1r) and agouti as candidates for dominant black in dogs. J Hered 2003; 94: 75–79.
89. Aldred PM, Hollox EJ, Armour JA. Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3. Hum Mol Genet 2005; 14: 2045–2052.
90. Morrison G, Kilanowski F, Davidson D, Dorin J. Characterization of the mouse beta defensin 1, Defb1, mutant mouse model. Infect Immun 2002; 70: 3053–3060.
91. Moser C, Weiner DJ, Lysenko E, Bals R, Weiser JN, Wilson JM. Beta-defensin 1 contributes to pulmonary innate immunity in mice. Infect Immun 2002; 70: 3068–3072.
92. Sinha PS, Schioth HB, Tatro JB. Activation of central melanocortin-receptor suppresses lipopolysaccharide-induced fever in rats. Am J Physiol Regul Integr Comp Physiol 2003; 284: R1595– R1603.
93. Tatro JB, Sinha PS. The central melanocortin system and fever. Ann N Y Acad Sci 2003; 994: 246–257.
94. Catania A, Gatti S, Colombo G, Lipton JM. Alpha-melanocyte stimulating hormone in modulation of inflammatory reactions. Pediatr Endocrinol Rev 2003; 1: 101–108.
95. Catania A, Gatti S, Colombo G, Lipton JM. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev 2004; 56: 1–29.
96. Luger TA, Scholzen TE, Brzoska T, Bohm M. New insights into the functions of alpha-MSH and related peptides in the immune system. Ann N Y Acad Sci 2003; 994: 133–140.
97. Lechan RM, Tatro JB. Hypothalamic melanocortin signaling in cachexia. Endocrinology 2001; 142: 3288–3291.
98. Marks DL, Butler AA, Turner R, Brookhart G, Cone RD. Differential role of melanocortin receptor subtypes in cachexia. Endocrinology 2003; 144: 1513–1523.
99. Wisse BE, Frayo RS, Schwartz MW, Cummings DE. Reversal of cancer anorexia by blockade of central melanocortin receptors in rats. Endocrinology 2001; 142: 3292–3301.
100. de Wied D. Melanotropins as neuropeptides. Ann N Y Acad Sci 1993; 680: 20–28.
101. de Wied D. Inhibitory effect of ACTH and related peptides on extinction of conditioned avoidance behavior in rats. Proc Soc Exp Biol Med 1966; 122: 28–32.
102. Bohus B, De Wied D. Inhibitory and facilitatory effect of two related peptides on extinction of avoidance behavior. Science 1966; 153: 318–320.
103. Ferrari W, Gessa GL, Vargiu L. Behavioral effects induced by intracisternally injected ACTH and MSH. Ann N Y Acad Sci 1963; 104: 330–345.
104. Lipton JM, Glyn JR, Zimmer JA. ACTH and alpha-melanotropin in central temperature control. Fed Proc 1981; 40: 2760–2764.