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.
|Data di pubblicazione:||2003|
|Titolo:||Functional role, structure, and evolution of the melanocortin-4 receptor|
|Autore/i:||Hb, Schioth; Mc, Lagerstrom; H., Watanobe; L., Jonsson; Vergoni, Anna Valeria; A., Ringholm; Jo, Skarphedinsson; Gv, Skuladottir; J., Klovins; R., Fredriksson|
|Codice identificativo ISI:||WOS:000184303800009|
|Codice identificativo Scopus:||2-s2.0-0038051138|
|Codice identificativo Pubmed:||12851300|
|Citazione:||Functional role, structure, and evolution of the melanocortin-4 receptor / Hb, Schioth; Mc, Lagerstrom; H., Watanobe; L., Jonsson; Vergoni, Anna Valeria; A., Ringholm; Jo, Skarphedinsson; Gv, Skuladottir; J., Klovins; R., Fredriksson. - In: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. - ISSN 0077-8923. - STAMPA. - 994(2003), pp. 74-83.|
|Tipologia||Articolo su rivista|
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