Parks Gregory S, Wang Lien, Wang Zhiwei, Civelli Olivier
Department of Pharmacology, University of California Irvine, Irvine, California, 92697; Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, 92697.
J Comp Neurol. 2014 Dec 1;522(17):3817-33. doi: 10.1002/cne.23642. Epub 2014 Jul 17.
Melanin-concentrating hormone (MCH) is a 19-amino-acid cyclic neuropeptide that acts in rodents via the MCH receptor 1 (MCHR1) to regulate a wide variety of physiological functions. MCH is produced by a distinct population of neurons located in the lateral hypothalamus (LH) and zona incerta (ZI), but MCHR1 mRNA is widely expressed throughout the brain. The physiological responses and behaviors regulated by the MCH system have been investigated, but less is known about how MCH neurons are regulated. The effects of most classical neurotransmitters on MCH neurons have been studied, but those of most neuropeptides are poorly understood. To gain insight into how neuropeptides regulate the MCH system, we investigated which neuropeptide receptors are expressed by MCH neurons by using double in situ hybridization. In all, 20 receptors, selected based on either a suspected interaction with the MCH system or demonstrated high expression levels in the LH and ZI, were tested to determine whether they are expressed by MCH neurons. Overall, 11 neuropeptide receptors were found to exhibit significant colocalization with MCH neurons: nociceptin/orphanin FQ opioid receptor (NOP), MCHR1, both orexin receptors (ORX), somatostatin receptors 1 and 2 (SSTR1, SSTR2), kisspeptin recepotor (KissR1), neurotensin receptor 1 (NTSR1), neuropeptide S receptor (NPSR), cholecystokinin receptor A (CCKAR), and the κ-opioid receptor (KOR). Among these receptors, six have never before been linked to the MCH system. Surprisingly, several receptors thought to regulate MCH neurons displayed minimal colocalization with MCH, suggesting that they may not directly regulate the MCH system.
黑色素聚集激素（MCH）是一种由19个氨基酸组成的环状神经肽，在啮齿动物中通过MCH受体1（MCHR1）发挥作用，调节多种生理功能。MCH由位于下丘脑外侧区（LH）和未定带（ZI）的一群独特神经元产生，但MCHR1 mRNA在全脑广泛表达。人们已经研究了MCH系统调节的生理反应和行为，但对MCH神经元如何被调节了解较少。大多数经典神经递质对MCH神经元的作用已被研究，但大多数神经肽的作用却知之甚少。为深入了解神经肽如何调节MCH系统，我们通过双重原位杂交研究了MCH神经元表达哪些神经肽受体。总共测试了20种受体，这些受体是基于与MCH系统的疑似相互作用或在LH和ZI中显示的高表达水平而选择的，以确定它们是否由MCH神经元表达。总体而言，发现11种神经肽受体与MCH神经元有显著共定位：孤啡肽/孤啡肽FQ阿片受体（NOP）、MCHR1、两种食欲素受体（ORX）、生长抑素受体1和2（SSTR1、SSTR2）、亲吻素受体（KissR1）、神经降压素受体1（NTSR1）、神经肽S受体（NPSR）、胆囊收缩素受体A（CCKAR）和κ-阿片受体（KOR）。在这些受体中，有六种此前从未与MCH系统相关联。令人惊讶的是，一些被认为调节MCH神经元的受体与MCH的共定位极少，这表明它们可能不直接调节MCH系统。
