Oosterom J, Burbach J P, Gispen W H, Adan R A
Rudolf Magnus Institute for Neurosciences, Medical Faculty, Utrecht University, Netherlands.
Eur J Pharmacol. 1998 Jul 31;354(1):R9-11. doi: 10.1016/s0014-2999(98)00491-9.
The melanocortin MC3 and MC4 receptors are the main melanocortin receptors expressed in brain. Of the endogenous melanocortins, gamma2-melanocortin stimulating hormone (MSH) selectively activates the melanocortin MC3 receptor, whereas alpha- and beta-MSH activate all melanocortin receptors. The aim was to gain an insight into the contribution of amino acids in positions 5 and 10 of melanocortins to the selectivity of [Nle4]Lys-gamma2-MSH for the melanocortin MC3 receptor versus the melanocortin MC4 receptor. Introduction of Asp10 into [Nle4]alpha-MSH as in [Nle4,Gly5,Asp10]alpha-MSH selectively increased the EC50 value for the melanocortin MC4 receptor. Conversely, removal of Asp10, as in [Nle4,Gly10]Lys-gamma2-MSH, selectively decreased the EC50 value for the melanocortin MC4 receptor. Thus, Asp10 in Lys-gamma2-MSH determined selectivity for the melanocortin MC3 receptor versus the melanocortin MC4 receptor.
黑皮质素MC3和MC4受体是大脑中表达的主要黑皮质素受体。在内源性黑皮质素中，γ2-促黑皮质素（MSH）选择性激活黑皮质素MC3受体，而α-和β-MSH激活所有黑皮质素受体。目的是深入了解黑皮质素第5位和第10位氨基酸对[Nle4]Lys-γ2-MSH对黑皮质素MC3受体与黑皮质素MC4受体选择性的贡献。如在[Nle4,Gly5,Asp10]α-MSH中将Asp10引入[Nle4]α-MSH中，选择性增加了黑皮质素MC4受体的EC50值。相反，如在[Nle4,Gly10]Lys-γ2-MSH中去除Asp10，选择性降低了黑皮质素MC4受体的EC50值。因此，Lys-γ2-MSH中的Asp10决定了对黑皮质素MC3受体与黑皮质素MC4受体的选择性。
