Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors.
There are five known members of the melanocortin receptor system each with differing specificities for melanocortins:
. MC1R is associated with pigmentation genetics. . MC2R is also known as the ACTH receptor or corticotropin receptor because it is specific for ACTH alone. . MC3R is associated with childhood growth, accrual of lean mass and onset of puberty.Lam, B.Y.H., Williamson, A., Finer, S. et al. MC3R links nutritional state to childhood growth and the timing of puberty. Nature (2021). . Defects in MC4R are a cause of autosomal dominant obesity, accounting for 6% of all cases of early-onset obesity. . MC5R These receptors are inhibited by endogenous inverse agonists agouti signalling peptide and agouti-related peptide, and activated by synthetic (i.e. afamelanotide) and endogenous agonist melanocyte-stimulating hormones.
Selective ligands Several selective ligands for the melanocortin receptors are known, and some synthetic compounds have been investigated as potential tanning, anti-obesity and aphrodisiac drugs, with tanning effects mainly from stimulation of MC1, while anorectic and aphrodisiac effects appear to involve both MC3 and MC4. MC1, MC3 and MC4 are widely expressed in the brain, and are also thought to be responsible for effects on mood and cognition.
Agonists Non-selective α-MSH β-MSH γ-MSH Afamelanotide Bremelanotide Melanotan II Modimelanotide Setmelanotide
MC1-selective BMS-470,539
MC4-selective PF-00446687 PL-6983 THIQ
Unknown (but for certain MC2-acting) Alsactide Tetracosactide
Antagonists and inverse agonists Non-selective Agouti-related peptide Agouti signalling peptide
MC2-selective Atumelnant (CRN04894)
MC4-selective HS-014 HS-024 MCL-0042 MCL-0129 MPB-10 SHU-9119 (agonist at MC1 and MC5, antagonist at MC3 and MC4)
Unknown Semax
References
External links
Calculated spatial position of melanocortin-4 receptor in the lipid bilayer, inactive state with antagonist and active state with agonist