Document Detail


Molecular cloning, pharmacological characterization, and brain mapping of the melanocortin 4 receptor in the goldfish: involvement in the control of food intake.
MedLine Citation:
PMID:  12746294     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
José Miguel Cerdá-Reverter; Aneta Ringholm; Helgi Birgir Schiöth; Richard Ector Peter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Endocrinology     Volume:  144     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-05-14     Completed Date:  2003-06-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2336-49     Citation Subset:  AIM; IM    
Affiliation:
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, T6G 2E9 Canada. cerdarev@iats.csic.es
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MeSH Terms
Descriptor/Qualifier:
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:
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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