The human melanocyte stimulating hormone receptor has evolved to become “super-sensitive” to melanocortin peptides

Abstract

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 ( EC 50 = 1–2 pM) to the super potent analogue of α-MSH, NDP-MSH. In contrast with the mMCl-R, the hMCl-R is also very sensitive to α-MSH ( EC 50 = 2 pM), ACTH ( EC 50 = 8 pM), and Lysγ 3-MSH ( EC 50 < 10 −10 M). This suggests that in man, in contrast with rodents, both ACTH and Lysγ 3-MSH may have physiological roles in pigmentation.