PUBLICATION
Functional role, structure, and evolution of the melanocortin-4 receptor
- Authors
- Schiöth, H.B., Lagerström, M.C., Watanobe, H., Jonsson, L., Vergoni, A.V., Ringholm, A., Skarphedinsson, J.O., Skuladottir, G.V., Klovins, J., and Fredriksson, R.
- ID
- ZDB-PUB-030716-3
- Date
- 2003
- Source
- Annals of the New York Academy of Sciences 994: 74-83 (Journal)
- Registered Authors
- Fredriksson, Robert, Ringholm, Aneta
- Keywords
- none
- MeSH Terms
-
- Animals
- Eating*
- Humans
- Hypothalamus/metabolism
- Metals/metabolism
- Phylogeny
- Receptor, Melanocortin, Type 4
- Receptors, Corticotropin/chemistry
- Receptors, Corticotropin/classification
- Receptors, Corticotropin/genetics
- Receptors, Corticotropin/metabolism*
- Reproduction/physiology
- alpha-MSH/agonists
- alpha-MSH/metabolism
- PubMed
- 12851300 Full text @ Ann N Y Acad Sci
Citation
Schiöth, H.B., Lagerström, M.C., Watanobe, H., Jonsson, L., Vergoni, A.V., Ringholm, A., Skarphedinsson, J.O., Skuladottir, G.V., Klovins, J., and Fredriksson, R. (2003) Functional role, structure, and evolution of the melanocortin-4 receptor. Annals of the New York Academy of Sciences. 994:74-83.
Abstract
The melanocortin (MC)-4 receptor participates in regulating body weight homeostasis. We demonstrated early that acute blockage of the MC-4 receptor increases food intake and relieves anorexic conditions in rats Our recent studies show that 4-week chronic blockage of the MC-4 receptor leads to robust increases in food intake and development of obesity, whereas stimulation of the receptor leads to anorexia. Interestingly, the food conversion ratio was clearly increased by MC-4 receptor blockage, whereas it was decreased in agonist-treated rats in a transient manner. Chronic infusion of an agonist caused a transient increase in oxygen consumption. Our studies also show that the MC-4 receptor plays a role in luteinizing hormone and prolactin surges in female rats. The MC-4 receptor has a role in mediating the effects of leptin on these surges. The phylogenetic relation of the MC-4 receptor to other GPCRs in the human genome was determined. The three-dimensional structure of the protein was studied by construction of a high-affinity zinc binding site between the helices, using two histidine residues facing each other. We also cloned the MC-4 receptor from evolutionary important species and showed by chromosomal mapping a conserved synteny between humans and zebrafish. The MC-4 receptor has been remarkably conserved in structure and pharmacology for more than 400 million years , implying that the receptor participated in vital physiological functions early in vertebrate evolution.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping