The human melanocyte stimulating hormone receptor has evolved to become "super-sensitive" to melanocortin peptides.
Melanocyte-stimulating hormone (MSH) stimulates pigmentation in mammals by activating specific cell surface MSH receptors (MC1-Rs) on melanocytes. MC1-Rs on normal human melanocytes have been difficult to detect and characterise. The pharmacological characterisation of a cloned human MC1-R (hMC1-R) is reported here, and directly compared with that of a cloned mouse MC1-R (mMC1-R). The human and mouse MC1-Rs are equally sensitive (EC50 = 1-2 pM) to the super potent analogue of alpha-MSH, NDP-MSH. In contrast with the mMC1-R, the hMC1-R is also very sensitive to alpha-MSH (EC50 = 2 pM), ACTH (EC50 = 8 pM), and Lys gamma 3-MSH (EC50 < 10(-10) M). This suggests that in man, in contrast with rodents, both ACTH and Lys gamma 3-MSH may have physiological roles in pigmentation.
Mountjoy
K G
KG
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201-3098.
D000262:Adenylyl Cyclases / Q000096:biosynthesis / Q000187:drug effects; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D018076:DNA, Complementary; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011979:Receptors, Pituitary Hormone / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D018076:DNA, Complementary; D011979:Receptors, Pituitary Hormone; C029446:MSH receptor; D009074:Melanocyte-Stimulating Hormones; D000262:Adenylyl Cyclases