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.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Schiöth HB,Lagerström MC,Watanobe H,Jonsson L,Vergoni AV,Ringholm A,Skarphedinsson JO,Skuladottir GV,Klovins J,Fredriksson Rdoi
10.1111/j.1749-6632.2003.tb03164.xsubject
Has Abstractpub_date
2003-06-01 00:00:00pages
74-83eissn
0077-8923issn
1749-6632journal_volume
994pub_type
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