Melanin-concentrating hormone (MCH) is a cyclic peptide highly conserved in vertebrates and was originally identified as a skin-paling factor in Teleosts. In fishes, MCH also participates in the regulation of the stress-response and feeding behaviour. Mammalian MCH is a hypothalamic neuropeptide that displays multiple functions, mostly controlling feeding behaviour and energy homeostasis. Transgenic mouse models and pharmacological studies have shown the importance of the MCH system as a potential target in the treatment of appetite disorders and obesity as well as anxiety and psychiatric diseases. Two G-protein-coupled receptors (GPCRs) binding MCH have been characterized so far. The first, named MCH-R1 and also called SLC1, was identified through reverse pharmacology strategies by several groups as a cognate receptor of MCH. This receptor is expressed at high levels in many brain areas of rodents and primates and is also expressed in peripheral organs, albeit at a lower rate. A second receptor, designated MCH-R2, exhibited 38% identity to MCH-R1 and was identified by sequence analysis of the human genome. Interestingly, although MCH-R2 orthologues were also found in fishes, dogs, ferrets and non-human primates, this MCH receptor gene appeared either lacking or non-functional in rodents and lagomorphs. Both receptors are class I GPCRs, whose main roles are to mediate the actions of peptides and neurotransmitters in the central nervous system. However, examples of action of MCH on neuronal and non-neuronal cells are emerging that illustrate novel MCH functions. In particular, the functionality of endogenously expressed MCH-R1 has been explored in human neuroblastoma cells, SK-N-SH and SH-SY5Y cells, and in non-neuronal cell types such as the ependymocytes. Indeed, we have identified mitogen-activated protein kinase (MAPK)-dependent or calcium-dependent signalling cascades that ultimately contributed to neurite outgrowth in neuroblastoma cells or to modulation of ciliary beating in ependymal cells. The putative role of MCH on cellular shaping and plasticity on one side and volume transmission on the other must be now considered.

黑色素浓缩激素 (MCH) 是一种在脊椎动物中高度保守的环肽，最初被确定为硬骨鱼中的一种皮肤变白因子。在鱼类中，MCH 还参与调节应激反应和摄食行为。哺乳动物 MCH 是一种下丘脑神经肽，具有多种功能，主要控制摄食行为和能量稳态。转基因小鼠模型和药理学研究表明，MCH 系统作为治疗食欲障碍和肥胖症以及焦虑症和精神疾病的潜在靶标的重要性。迄今为止，已经对两种结合 MCH 的 G 蛋白偶联受体 (GPCR) 进行了表征。第一个，命名为 MCH-R1，也称为 SLC1，被多个小组通过反向药理学策略鉴定为 MCH 的同源受体。该受体在啮齿动物和灵长类动物的许多脑区中高水平表达，并且在外周器官中也有表达，尽管速度较低。第二种受体，称为 MCH-R2，与 MCH-R1 具有 38% 的同一性，并通过人类基因组的序列分析鉴定。有趣的是，虽然在鱼类、狗、雪貂和非人类灵长类动物中也发现了 MCH-R2 直系同源物，但这种 MCH 受体基因在啮齿动物和兔类动物中似乎缺乏或没有功能。这两种受体都是 I 类 GPCR，其主要作用是介导中枢神经系统中肽和神经递质的作用。然而，MCH 对神经元和非神经元细胞的作用的例子正在出现，这些例子说明了新的 MCH 功能。尤其，已在人类神经母细胞瘤细胞、SK-N-SH 和 SH-SY5Y 细胞以及非神经元细胞类型（如室管膜细胞）中探索了内源性表达的 MCH-R1 的功能。事实上，我们已经确定了丝裂原活化蛋白激酶 (MAPK) 依赖性或钙依赖性信号级联反应，这些级联反应最终导致神经母细胞瘤细胞中的神经突生长或调节室管膜细胞中的纤毛跳动。现在必须考虑 MCH 在一方面对细胞形状和可塑性以及另一方面对体积传递的推定作用。我们已经确定了丝裂原活化蛋白激酶 (MAPK) 依赖性或钙依赖性信号级联反应，最终导致神经母细胞瘤细胞中的神经突生长或调节室管膜细胞中的纤毛跳动。现在必须考虑 MCH 在一方面对细胞形状和可塑性以及另一方面对体积传递的推定作用。我们已经确定了丝裂原活化蛋白激酶 (MAPK) 依赖性或钙依赖性信号级联反应，最终导致神经母细胞瘤细胞中的神经突生长或调节室管膜细胞中的纤毛跳动。现在必须考虑 MCH 在一方面对细胞形状和可塑性以及另一方面对体积传递的推定作用。