Pharmacological comparison of rat and human melanocortin 3 and 4 receptors in vitro.
The melanocortin 3 and 4 receptors are G-protein-coupled receptors found in the hypothalamus with important role in regulation of the energy balance. In this study, we performed pharmacological comparison of the rat and human melancortin (MC) 3 and MC4 receptors. We transiently expressed the genes for these receptors individually in a mammalian cell line and determined the binding affinities to several MSH peptides. The results showed no major difference between the rat and human MC3 receptors while the rat MC4 receptor had higher affinity to several peptides compared with the human MC4 receptor. NDP-, alpha-, beta-, gamma-MSH, ACTH(1-24), HS014 and MTII had from 5- to 34-fold higher affinity for the rat MC4 receptor, while SHU9119, HS024 and HS028 had similar affinity for both the MC4 receptors. Pharmacological species difference have earlier been reported for the MC1 and MC5 receptors but this is the first report showing important differences between the rat and human MC4 receptors.
Schiöth
Helgi B
HB
Department of Neuroscience, Biomedical Center, Box 593, 751 24 Uppsala University, Uppsala, Sweden. helgis@bmc.uu.se
Bouifrouri
Amin A
AA
Rudzish
Richard
R
Muceniece
Ruta
R
Watanobe
Hajime
H
Wikberg
Jarl E S
JE
Larhammar
Dan
D
D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding; D051381:Rats; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000235:genetics / Q000378:metabolism*; D000521:alpha-MSH / Q000378:metabolism / Q000494:pharmacology
D008024:Ligands; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D000521:alpha-MSH; D000242:Cyclic AMP