Body weight regulation by selective MC4 receptor agonists and antagonists

Annals of the New York Academy of Sciences

Volumn 994, Issue , 2003, Pages 103-110

  Foster, Alan C ^a   Joppa, Margaret ^a   Markison, Stacy ^a   Gogas, Kathy R ^a   Fleck, Beth A ^a   Murphy, Brian J ^a   Wolff, Meira ^a   Cismowski, Mary J ^a   Ling, Nicholas ^a   Goodfellow, Val S ^a   Chen, Chen ^a   Saunders, John ^a   Conlon, Paul J ^a  

^a NEUROCRINE BIOSCIENCES INC   (United States)

Author keywords

Cachexia; MC4; Melanocortin receptor; Obesity; Selective agonist; Selective antagonist

Indexed keywords

AGOUTI RELATED PROTEIN; AGOUTI RELATED PROTEIN[83-132]; ALPHA INTERMEDIN; ANOREXIGENIC AGENT; BETA INTERMEDIN[11-22][11 (N ACETYLCYSTEINE) 14 (3,4 DICHLORO DEXTRO PHENYLALANINE) 18 CYSTEINE 22 ASPARTIC ACID AMIDE] 11,18 CYCLIC DISULFIDE; BETA INTERMEDIN[11-22][11 (N ACETYLCYSTEINE) 14 [3 (2 NAPHTHYL) DEXTRO ALANINE] 18 CYSTEINE 22 ASPARTIC ACID AMIDE] 11,18 CYCLIC DISULFIDE; CORTICOTROPIN; CYCLOPEPTIDE; CYCLOPEPTIDE C [1-6] SUCCINYLPHENYLALANYLARGINYLTRYPTOPHYLLYSINAMIDE; GAMMA INTERMEDIN; HORMONE RECEPTOR AFFECTING AGENT; MBP 10; MELANOCORTIN 1 RECEPTOR; MELANOCORTIN 3 RECEPTOR; MELANOCORTIN 4 RECEPTOR; MELANOCORTIN 4 RECEPTOR BLOCKING AGENT; MELANOCORTIN 4 RECEPTOR STIMULATING AGENT; MELANOCORTIN 5 RECEPTOR; MT II; N ACETYL ALPHA INTERMEDIN[4-10]CYCLO[4 NORLEUCINE 5 ASPARTIC ACID 7 [3 (2 NAPHTHYL)ALANINE] 10 LYSINAMIDE]; PEPTIDE DERIVATIVE; RO 27 3225; RO 27 4680; RO 27 4684; UNCLASSIFIED DRUG;

BODY WEIGHT; CACHEXIA; CONFERENCE PAPER; DRUG EFFECT; DRUG POTENCY; DRUG SELECTIVITY; GENETIC ANALYSIS; NONHUMAN; OBESITY; PHARMACOLOGICAL BLOCKING; PHARMACOLOGICAL STIMULATION; RECEPTOR AFFINITY; RECEPTOR BLOCKING; RECEPTOR UPREGULATION; REGULATORY MECHANISM;

AGOUTI;

EID: 0037713324     PISSN: 00778923     EISSN: None     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.2003.tb03168.x     Document Type: Conference Paper

References (31)

1. MACNEIL, D.J. et al. 2002. The role of melanocortins in body weight regulation: opportunities for the treatment of obesity. Eur. J. Pharmacol. 450: 93-109.
2. MARKS, D.L. et al. 2002. Melanocortin pathways: animal models of obesity and disease. Ann. Endocrinol. 63: 121-124.
3. LU, D. et al. 1994. Agouti protein is an antagonist of the melanoortin-stimulating hormone receptor. Nature 371: 799-802.
4. SHUTTER, J.R. et al. 1997. Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes Dev. 11: 593-602.
5. OLLMANN, M.M. et al. 1997. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278: 135-138.
6. HUSZAR, D. et al. 1997. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88: 131-141.
7. BUTLER, A.A. et al. 2000. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 141: 3518-3521.
8. CHEN, A.S. et al. 2000. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat. Genet. 26: 97-102.
9. YASWEN, L. et al. 1999. Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat. Med. 5: 1066-1070.
10. QIAN, S. et al. 2002. Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Mol. Cell. Biol. 22: 5027-5035.
11. KRUDE, et al. 1998. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat. Genet. 19: 155-157.
12. FAROOQI, I.S. et al. 2000. Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J. Clin. Invest. 106: 271-279.
13. VAISSE, C. et al. 2000. Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J. Clin. Invest. 106: 253-262.
14. FAN, W. et al. 1997. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 385: 165-168.
15. KOEGLER, F.H. et al. 2001. Central melanocortin receptors mediate changes in food intake in the rhesus macaque. Endocrinology 142: 2586-2592.
16. JONSSON, L. et al. 2002. Food conversion is transiently affected during 4-week chronic administration of melanocortin agonist and antagonist in rats. J. Endocrinol. 173: 517-523.
17. LU, X.Y. et al. 2001. Time course of short-term and long-term orexigenic effects of agouti-related protein (86-132). Neuroreport 12: 1281-1284.
18. RAPOSINHO, P.D. et al. 2000. Chronic blockade of the melanocortin 4 receptor subtype leads to obesity independently of neuropeptide Y action, with no adverse effects on the gonadotropic and somatotropic axes. Endocrinology 141: 4419-4427.
19. TISDALE, M.J. 1997. Biology of cachexia. J. Natl. Cancer Inst. 89: 1763-1773.
20. PLATA-SALAMAN, C.R. 2000. Central nervous system mechanisms contributing to the cancer-anorexia syndrome. Nutrition 16: 1009-1012.
21. HUANG, Q-H. et al. 1999. Role of central melanocortins in endotoxin-induced anorexia. Am. J. Physiol. 276: R864-R871.
22. MARKS, D.L. et al. 2001. Role of central melanocortin system in cachexia. Cancer Res. 61: 1432-1438.
23. WISSE, B.E. et al. 2001. Reversal of cancer anorexia by blockade of central melanocortin receptors in rats. Endocrinology 142: 3292-3301.
24. VERGONI, A.V. et al. 1999. Selective melanocortin MC4 receptor blockade reduces immobilization stress-induced anorexia in rats. Eur. J. Pharmacol. 369: 11-15.
25. MARSH, D.J. et al. 1999. Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Nat. Genet. 21: 119-122.
26. BENOIT, S.C. et al. 2000. A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. J. Neurosci. 20: 3442-3448.
27. VERGONI, A.V. et al. 2000. Chronic melanocortin 4 receptor blockage causes obesity without influencing sexual behavior in male rats. J. Endocrinol. 166: 419-426.
28. SKULADOTTIR, G.V. et al. 1999. Long-term orexigenic effect of a novel melanocortin 4 receptor selective antagonist. Br. J. Pharmacol. 126: 27-34.
29. BEDNAREK, M.A. et al. 2001. Potent and selective peptide agonists of α-melanotropin action at human melanocortin receptor 4: their synthesis and biological evaluation in vitro. Biochem. Biophys. Res. Commun. 286: 641-645.
30. BEDNAREK, M.A. et al. 2001. Elective, high affinity peptide antagonists of α-melanotropin action at human melanocortin receptor 4: their synthesis and biological evaluation in vitro. J. Med. Chem. 44: 3665-3672.
31. GOODFELLOW, V.S. & J. SAUNDERS. 2003. The melanocortin system and its role in obesity and cachexia. Curr. Top. Med. Chem. 3: 855-883.