[苯丙氨酸-I7]、[丙氨酸6]和[D-丙氨酸4、谷氨酰胺5、酪氨酸6]取代的促肾上腺皮质激素(4-10)类似物对黑皮质素受体的选择性。

Selectivity of [Phe-I7], [Ala6], and [D-Ala4,Gln5,Tyr6] substituted ACTH(4-10) analogues for the melanocortin receptors.

作者信息

Schiöth H B, Muceniece R, Wikberg J E

机构信息

Department of Pharmaceutical Pharmacology, Uppsala University, Sweden.

出版信息

Peptides. 1997;18(5):761-3. doi: 10.1016/s0196-9781(97)00126-5.

DOI:10.1016/s0196-9781(97)00126-5

PMID:9213373

Abstract

We tested [Ala6]ACTH(4-10) and [Phe-I7]ACTH(4-10)(putative MC receptor antagonists), [D-Ala4,Gln5,Tyr6]ACTH(4-10)(BIM 22015), and ACTH (4-10) with radioligand binding using transiently expressed human MC1, MC3, MC4, and MC3 receptors. [Phe-I7]ACTH(4-10) had higher affinity for the MC3, MC4, and MC3 receptors but lower for the MC1 compared to ACTH(4-10). [Ala6]ACTH(4-10) did not bind the MC1 receptor but had highest affinity for the MC4 receptor. The data indicate that the His6 has a specially important role in binding to the MC1 receptor. The BIM 22015 did not bind to these MC receptor subtypes, which indicates that the neurotrophic and myotrophic properties that are attributed to this peptide are mediated by some other receptor.

摘要

我们使用瞬时表达的人MC1、MC3、MC4和MC3受体，通过放射性配体结合试验检测了[丙氨酸6]促肾上腺皮质激素（4-10）和[苯丙氨酸-I7]促肾上腺皮质激素（4-10）（假定的MC受体拮抗剂）、[D-丙氨酸4，谷氨酰胺5，酪氨酸6]促肾上腺皮质激素（4-10）（BIM 22015）以及促肾上腺皮质激素（4-10）。与促肾上腺皮质激素（4-10）相比，[苯丙氨酸-I7]促肾上腺皮质激素（4-10）对MC3、MC4和MC3受体具有更高的亲和力，但对MC1受体的亲和力较低。[丙氨酸6]促肾上腺皮质激素（4-10）不与MC1受体结合，但对MC4受体具有最高的亲和力。数据表明，组氨酸6在与MC1受体结合中具有特别重要的作用。BIM 22015不与这些MC受体亚型结合，这表明归因于该肽的神经营养和肌营养特性是由其他一些受体介导的。