黑皮质素MC3、MC4和MC5受体拮抗剂的鉴定。

Identification of antagonists for melanocortin MC3, MC4 and MC5 receptors.

作者信息

Adan R A, Oosterom J, Ludvigsdottir G, Brakkee J H, Burbach J P, Gispen W H

机构信息

Department of Medical Pharmacology, Utrecht University, Netherlands.

出版信息

Eur J Pharmacol. 1994 Nov 15;269(3):331-7. doi: 10.1016/0922-4106(94)90041-8.

DOI:10.1016/0922-4106(94)90041-8

PMID:7895772

Abstract

Antagonists for the melanocortin receptor family were identified by analysis of the effects of four melanocortin analogues on alpha-MSH(alpha-melanocyte-stimulating hormone)-induced cAMP accumulation in 293 human embryonal kidney (HEK) cells that expressed either the rat melanocortin MC3 receptor, the human melanocortin MC4 receptor or the ovine melanocortin MC5 receptor. Two peptides, [D-Arg8]ACTH(adrenocorticotrope hormone)-(4-10) and [Pro8,10,Gly9]ACTH-(4-10), antagonized the action of alpha-MSH on the melanocortin MC4 and MC5 receptors, but not the melanocortin MC3 receptor. [Ala6]ACTH-(4-10) inhibited the alpha-MSH activation of the melanocortin MC3 and MC5, but only weakly antagonized the activation of the melanocortin MC4 receptor. [Phe-I7]ACTH-(4-10) antagonized the melanocortin MC3, MC4 and MC5 receptors equally well. These antagonists were also tested to block a behavioral response induced by alpha-MSH. alpha-MSH-induced excessive grooming behavior in rats was inhibited by [Phe-I7]ACTH-(4-10), [D-Arg8]ACTH-(4-10) and [Pro8,10,Gly9]ACTH-(4-10), but not by [Ala6]ACTH-(4-10). This suggests that alpha-MSH-induced excessive grooming behavior is mediated by melanocortin MC4 receptors.

摘要

通过分析四种促黑素类似物对表达大鼠促黑素MC3受体、人促黑素MC4受体或羊促黑素MC5受体的293人胚肾（HEK）细胞中α-MSH（α-黑素细胞刺激素）诱导的环磷酸腺苷（cAMP）积累的影响，确定了促黑素受体家族的拮抗剂。两种肽，[D-精氨酸8]促肾上腺皮质激素（ACTH）-（4-10）和[脯氨酸8,10，甘氨酸9]促肾上腺皮质激素-（4-10），拮抗α-MSH对促黑素MC4和MC5受体的作用，但不拮抗促黑素MC3受体。[丙氨酸6]促肾上腺皮质激素-（4-10）抑制促黑素MC3和MC5的α-MSH激活，但仅微弱拮抗促黑素MC4受体的激活。[苯丙氨酸-I7]促肾上腺皮质激素-（4-10）对促黑素MC3、MC4和MC5受体的拮抗作用同样良好。还测试了这些拮抗剂对α-MSH诱导的行为反应的阻断作用。[苯丙氨酸-I7]促肾上腺皮质激素-（4-10）、[D-精氨酸8]促肾上腺皮质激素-（4-10）和[脯氨酸8,10,甘氨酸9]促肾上腺皮质激素-（4-10）可抑制大鼠中α-MSH诱导的过度梳理行为，但[丙氨酸6]促肾上腺皮质激素-（4-10）则不能。这表明α-MSH诱导的过度梳理行为是由促黑素MC4受体介导的。