Department of Pharmacology, University of California, Irvine, USA.
Peptides. 2009 Nov;30(11):1985-9. doi: 10.1016/j.peptides.2009.07.017. Epub 2009 Aug 6.
Melanin-concentrating hormone (MCH) is a cyclic peptide which was originally discovered in fish to lighten skin color by affecting melanosomes aggregation. This peptide is highly conserved and also found in rodents whose gene is overexpressed upon fasting. However, the site of MCH action remained obscure until its receptor was discovered in 1999 as a G protein-coupled receptor. After this receptor structure was identified, the functional domains important for MCH-MCHR interaction were revealed. Moreover, the cloning of the MCH receptor led us to identify the in vivo sites of MCH action which suggested potential physiological functions of the MCH system. Furthermore, the MCH receptor identification allow for designing surrogate molecules which can block MCH activity. Studies using these molecules revealed various physiological functions of the MCH system not only in feeding but also in other physiological responses such as stress and emotion. This review will discuss how the MCH receptor was discovered and its impact on many studies investigating the MCH receptor's structure, signaling pathways, and expression pattern.
黑色素浓缩激素(MCH)是一种环状肽,最初在鱼类中发现,通过影响黑色素聚集来提亮肤色。这种肽高度保守,在啮齿动物中也有发现,其基因在禁食时会过度表达。然而,直到 1999 年发现其受体作为 G 蛋白偶联受体,MCH 的作用部位仍然不清楚。该受体结构确定后,揭示了 MCH-MCHR 相互作用的重要功能域。此外,MCH 受体的克隆使我们能够确定 MCH 的体内作用部位,这表明了 MCH 系统的潜在生理功能。此外,MCH 受体的鉴定允许设计能够阻断 MCH 活性的替代分子。使用这些分子的研究揭示了 MCH 系统的各种生理功能,不仅在进食方面,而且在应激和情绪等其他生理反应方面。这篇综述将讨论 MCH 受体是如何被发现的,以及它对许多研究 MCH 受体结构、信号通路和表达模式的影响。