| Molecular cloning, pharmacological characterization, and brain mapping of the melanocortin 4 receptor in the goldfish: involvement in the control of food intake. | |
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MedLine Citation:
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PMID: 12746294 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We report cloning, pharmacological characterization, tissue distribution, detailed brain mapping, and role in control of food intake of melanocortin 4 receptor in goldfish (gMC4R). The gMC4R protein has 68% identity with the human ortholog and is conserved in important functional domains. Pharmacological profiling showed similar affinities and potency order to hMC4R for MSH peptides, whereas MTII and HS024 were identified as high-affinity agonist and antagonist analogs, respectively. The gMC4R-mRNA was found in brain and some peripheral tissues including the ovary, gill, and spleen. Detailed MC4R-mRNA mapping showed expression in main neuroendocrine and food intake-controlling areas. High expression levels were found in the telencephalon, preoptic area, ventral thalamus, tuberal hypothalamus, and hypothalamic inferior lobe. By RT-PCR, low levels were also detected in the cerebellum, medulla, and spinal cord. Intracerebroventricular MTII administration inhibited food intake in 24-h fasted animals in a dose-dependent manner, whereas HS024 stimulated food intake in fed animals, suggesting that melanocortins exert a tonic inhibitory effect on food intake, which is mediated through central MC4R signaling. The conserved central expression pattern and physiological role in regulation of food intake for the MC4R suggests that neuronal pathways of the melanocortin system may be important for regulation of energy homeostasis in most vertebrates. |
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Authors:
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José Miguel Cerdá-Reverter; Aneta Ringholm; Helgi Birgir Schiöth; Richard Ector Peter |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Endocrinology Volume: 144 ISSN: 0013-7227 ISO Abbreviation: Endocrinology Publication Date: 2003 Jun |
Date Detail:
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Created Date: 2003-05-14 Completed Date: 2003-06-25 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 2336-49 Citation Subset: AIM; IM |
Affiliation:
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Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6G 2E9 Canada. cerdarev@iats.csic.es |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Base Sequence Binding, Competitive Brain Chemistry / physiology* Brain Mapping Cloning, Molecular Eating / physiology* Female Gene Expression / physiology Goldfish / physiology* Injections, Intraventricular Male Molecular Sequence Data Peptides, Cyclic / metabolism, pharmacology RNA, Messenger / analysis Receptor, Melanocortin, Type 4 Receptors, Corticotropin / genetics*, metabolism Species Specificity alpha-MSH / analogs & derivatives*, metabolism, pharmacology beta-MSH / metabolism, pharmacology gamma-MSH / metabolism, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/HS 024; 0/Peptides, Cyclic; 0/RNA, Messenger; 0/Receptor, Melanocortin, Type 4; 0/Receptors, Corticotropin; 0/alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-; 0/beta-MSH; 0/gamma-MSH; 581-05-5/alpha-MSH; 75921-69-6/MSH, 4-Nle-7-Phe-alpha- |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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