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Division of Endocrinology and Metabolic Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom W12 0NN
Address all correspondence and requests for reprints to: Prof. S. R. Bloom, Division of Endocrinology and Metabolic Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London, United Kingdom W12 0NN. E-mail: sbloom{at}rpms.ac.uk
Melanin-concentrating hormone (MCH) has recently been proposed as both a central stimulator and an inhibitor of food intake. To clarify its role, we investigated the effects of MCH and the prepro-MCH-derived peptide neuropeptide E-I injected intracerebroventricularly (icv) in rats. MCH (0.1515 µg) was injected icv at the beginning of the light phase. Food intake at 2 h showed a dose-dependent increase from 325 ± 7% of the control value (1.5-µg dose; P < 0.05) to 462 ± 30% of the control value (15-µg dose; P < 0.005). When 10 ng, 100 ng, and 5 µg MCH were injected icv at the beginning of the dark phase, only 5 µg stimulated feeding (166 ± 16% of the control value; P < 0.05). At no dose did MCH inhibit feeding. Twice daily icv injections of MCH (5 µg) caused an average 197 ± 9% increase in 2-h food intake for the first 5 days. Injections from days 68 did not stimulate feeding. Food intake and body weight at 24 h remained unchanged. Intracerbroventricular neuropeptide E-I had no effect on food intake alone and did not alter MCH-induced feeding. These studies show a dose-dependent stimulation of feeding by acute central administration of MCH. Tolerance is seen with chronic administration. These findings support a role for MCH in the immediate regulation of food intake, but not in body weight control.
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C. L. Chaffer and M. J. Morris The Feeding Response to Melanin-Concentrating Hormone Is Attenuated by Antagonism of the NPY Y1-Receptor in the Rat Endocrinology, January 1, 2002; 143(1): 191 - 197. [Abstract] [Full Text] [PDF] |
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C. R. Abbott, M. Rossi, A. M. Wren, K. G. Murphy, A. R. Kennedy, S. A. Stanley, A. N. Zollner, D. G. A. Morgan, I. Morgan, M. A. Ghatei, et al. Evidence of an Orexigenic Role for Cocaine- and Amphetamine-Regulated Transcript after Administration into Discrete Hypothalamic Nuclei Endocrinology, August 1, 2001; 142(8): 3457 - 3463. [Abstract] [Full Text] [PDF] |
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A. W. Sailer, H. Sano, Z. Zeng, T. P. McDonald, J. Pan, S.-S. Pong, S. D. Feighner, C. P. Tan, T. Fukami, H. Iwaasa, et al. Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R PNAS, June 7, 2001; (2001) 121170598. [Abstract] [Full Text] [PDF] |
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E. G. Kokkotou, N. A. Tritos, J. W. Mastaitis, L. Slieker, and E. Maratos-Flier Melanin-Concentrating Hormone Receptor Is a Target of Leptin Action in the Mouse Brain Endocrinology, February 1, 2001; 142(2): 680 - 686. [Abstract] [Full Text] [PDF] |
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B. E. Hawes, E. Kil, B. Green, K. O'Neill, S. Fried, and M. P. Graziano The Melanin-Concentrating Hormone Receptor Couples to Multiple G Proteins to Activate Diverse Intracellular Signaling Pathways Endocrinology, December 1, 2000; 141(12): 4524 - 4532. [Abstract] [Full Text] [PDF] |
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D. Macdonald, N. Murgolo, R. Zhang, J. P. Durkin, X. Yao, C. D. Strader, and M. P. Graziano Molecular Characterization of the Melanin-Concentrating Hormone/Receptor Complex: Identification of Critical Residues Involved in Binding and Activation Mol. Pharmacol., July 1, 2000; 58(1): 217 - 225. [Abstract] [Full Text] |
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B. A. Henry, A. J. Tilbrook, F. R. Dunshea, A. Rao, D. Blache, G. B. Martin, and I. J. Clarke Long-Term Alterations in Adiposity Affect the Expression of Melanin-Concentrating Hormone and Enkephalin But Not Proopiomelanocortin in the Hypothalamus of Ovariectomized Ewes Endocrinology, April 1, 2000; 141(4): 1506 - 1514. [Abstract] [Full Text] [PDF] |
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A. Inui Transgenic Approach to the Study of Body Weight Regulation Pharmacol. Rev., March 1, 2000; 52(1): 35 - 62. [Abstract] [Full Text] [PDF] |
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J. G. Mercer, K. M. Moar, A. W. Ross, N. Hoggard, and P. J. Morgan Photoperiod regulates arcuate nucleus POMC, AGRP, and leptin receptor mRNA in Siberian hamster hypothalamus Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2000; 278(1): R271 - R281. [Abstract] [Full Text] [PDF] |
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A. Inui Cancer Anorexia-Cachexia Syndrome: Are Neuropeptides the Key? Cancer Res., September 1, 1999; 59(18): 4493 - 4501. [Abstract] [Full Text] [PDF] |
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A. Viale, C. Ortola, G. Hervieu, M. Furuta, P. Barbero, D. F. Steiner, N. G. Seidah, and J.-L. Nahon Cellular Localization and Role of Prohormone Convertases in the Processing of Pro-melanin Concentrating Hormone in Mammals J. Biol. Chem., March 5, 1999; 274(10): 6536 - 6545. [Abstract] [Full Text] [PDF] |
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B. A. Henry, J. W. Goding, W. S. Alexander, A. J. Tilbrook, B. J. Canny, F. Dunshea, A. Rao, A. Mansell, and I. J. Clarke Central Administration of Leptin to Ovariectomized Ewes Inhibits Food Intake without Affecting the Secretion of Hormones from the Pituitary Gland: Evidence for a Dissociation of Effects on Appetite and Neuroendocrine Function Endocrinology, March 1, 1999; 140(3): 1175 - 1182. [Abstract] [Full Text] |
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S. P. Kalra, M. G. Dube, S. Pu, B. Xu, T. L. Horvath, and P. S. Kalra Interacting Appetite-Regulating Pathways in the Hypothalamic Regulation of Body Weight Endocr. Rev., February 1, 1999; 20(1): 68 - 100. [Abstract] [Full Text] |
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K. Meeran, D. OShea, C. M. B. Edwards, M. D. Turton, M. M. Heath, I. Gunn, S. Abusnana, M. Rossi, C. J. Small, A. P. Goldstone, et al. Repeated Intracerebroventricular Administration of Glucagon-Like Peptide-1-(7-36) Amide or Exendin-(9-39) Alters Body Weight in the Rat Endocrinology, January 1, 1999; 140(1): 244 - 250. [Abstract] [Full Text] |
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C. Peyron, D. K. Tighe, A. N. van den Pol, L. de Lecea, H. C. Heller, J. G. Sutcliffe, and T. S. Kilduff Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems J. Neurosci., December 1, 1998; 18(23): 9996 - 10015. [Abstract] [Full Text] [PDF] |
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N. A. Tritos, J. K. Elmquist, J. W. Mastaitis, J. S. Flier, and E. Maratos-Flier Characterization of Expression of Hypothalamic Appetite-Regulating Peptides in Obese Hyperleptinemic Brown Adipose Tissue-Deficient (Uncoupling Protein-Promoter-Driven Diphtheria Toxin A) Mice Endocrinology, November 1, 1998; 139(11): 4634 - 4641. [Abstract] [Full Text] [PDF] |
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D. S. Ludwig, K. G. Mountjoy, J. B. Tatro, J. A. Gillette, R. C. Frederich, J. S. Flier, and E. Maratos-Flier Melanin-concentrating hormone: a functional melanocortin antagonist in the hypothalamus Am J Physiol Endocrinol Metab, April 1, 1998; 274(4): E627 - E633. [Abstract] [Full Text] [PDF] |
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L. de Lecea, T. S. Kilduff, C. Peyron, X.-B. Gao, P. E. Foye, P. E. Danielson, C. Fukuhara, E. L. F. Battenberg, V. T. Gautvik, F. S. Bartlett II, et al. The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity PNAS, January 6, 1998; 95(1): 322 - 327. [Abstract] [Full Text] [PDF] |
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J. Zhu and C. R. Kahn Analysis of a peptide hormone-receptor interaction in the yeast two-hybrid system PNAS, November 25, 1997; 94(24): 13063 - 13068. [Abstract] [Full Text] [PDF] |
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N. Vrang, P. J. Larsen, J. T. Clausen, and P. Kristensen Neurochemical Characterization of Hypothalamic Cocaine -- Amphetamine-Regulated Transcript Neurons J. Neurosci., May 15, 1999; 19(10): RC5 - RC5. [Abstract] [Full Text] [PDF] |
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L. Borsu, F. Presse, and J.-L. Nahon The AROM Gene, Spliced mRNAs Encoding New DNA/RNA-binding Proteins Are Transcribed from the Opposite Strand of the Melanin-concentrating Hormone Gene in Mammals J. Biol. Chem., December 15, 2000; 275(51): 40576 - 40587. [Abstract] [Full Text] [PDF] |
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V. Audinot, P. Beauverger, C. Lahaye, T. Suply, M. Rodriguez, C. Ouvry, V. Lamamy, J. Imbert, H. Rique, J.-L. Nahon, et al. Structure-Activity Relationship Studies of Melanin-concentrating Hormone (MCH)-related Peptide Ligands at SLC-1, the Human MCH Receptor J. Biol. Chem., April 20, 2001; 276(17): 13554 - 13562. [Abstract] [Full Text] [PDF] |
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J. Hill, M. Duckworth, P. Murdock, G. Rennie, C. Sabido-David, R. S. Ames, P. Szekeres, S. Wilson, D. J. Bergsma, I. S. Gloger, et al. Molecular Cloning and Functional Characterization of MCH2, a Novel Human MCH Receptor J. Biol. Chem., June 1, 2001; 276(23): 20125 - 20129. [Abstract] [Full Text] [PDF] |
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S. Wang, J. Behan, K. O'Neill, B. Weig, S. Fried, T. Laz, M. Bayne, E. Gustafson, and B. E. Hawes Identification and Pharmacological Characterization of a Novel Human Melanin-concentrating Hormone Receptor, MCH-R2 J. Biol. Chem., September 7, 2001; 276(37): 34664 - 34670. [Abstract] [Full Text] [PDF] |
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D. J. Marsh, D. T. Weingarth, D. E. Novi, H. Y. Chen, M. E. Trumbauer, A. S. Chen, X.-M. Guan, M. M. Jiang, Y. Feng, R. E. Camacho, et al. Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism PNAS, March 5, 2002; 99(5): 3240 - 3245. [Abstract] [Full Text] [PDF] |
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A. W. Sailer, H. Sano, Z. Zeng, T. P. McDonald, J. Pan, S.-S. Pong, S. D. Feighner, C. P. Tan, T. Fukami, H. Iwaasa, et al. Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R PNAS, June 19, 2001; 98(13): 7564 - 7569. [Abstract] [Full Text] [PDF] |
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