Melanin Concentrating Hormone, salmon (MCH (salmon))
(Synonyms: 黑色素聚集激素肽,MCH (salmon)) 目录号 : GC31149黑色素浓缩激素鲑鱼 (MCH (salmon)) 是一种 19 个氨基酸的神经肽,最初在硬骨鱼的脑垂体中发现,可调节食物摄入、能量平衡、睡眠状态和心血管系统。
Cas No.:87218-84-6
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Kinase experiment: | Binding of 125I-labeled Melanin Concentrating Hormone (MCH) to MCHR1 and MCHR2 is measured by filtration binding assay. Membranes (10 μg protein) from transiently transfected HEK293-MCHR1 and HEK293-MCHR2 cells are mixed with 0-9.8 nM 125I-labeled MCH in the binding buffer (50 mM Hepes/10 mM MgCl内容2/2 mM EGTA; protease inhibitors, 0.1% BSA, pH 7.6). After incubation for 1 h at room temperature, membrane-bound 125I-labeled MCH is separated from the free 125I-labeled MCH by filtration through a 96-well GF/B plate on a Packard Filtermate Cell Harvester and ished with ice-cold binding buffer supplemented with 80 mM NaCl. Eighty microliters of scintillation liquid is added, and the radioactivity is counted on a Packard Microplate Topcount[1]. |
Animal experiment: | Rats[2]Both male Wistar and male Sprague-Dawley rats weighing between 310 and 370 g (age 8-11 weeks) are used in the study. All animals receive food which had the following dry weight composition: 64% carbohydrate, 22% protein, 4.3% fat, 4% cellulose and 5.5% ash. For chronic experiments, the rats are infused either with artificial CSF (0.5 μL/h) or MCH (8 μg/rat/day).Body weight and food intake are then recorded daily for 12 days[2].Mice[3]Male C57BL/6J mice is prepared for measurement of spontaneous motor activity. Melanin Concentrating Hormone (10 μg/day) or the vehicle is infused for 14 days under the regular diet-fed condition. Motor activity is measured during the last 3 days of the 14-day infusion by an activity monitoring system in home cages[3]. |
References: [1]. An S, et al. Identification and characterization of a melanin-concentrating hormone receptor. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7576-81. |
Melanin Concentrating Hormone, salmon is a 19-amino-acid neuropeptide initially identified in the pituitary gland of teleost fish, which regulates food intake, energy balance, sleep state, and the cardiovascular system. Melanin-concentrating hormone is a ligand for an orphan G protein-coupled receptor (SLC-1/GPR24) and MCHR2.
An orphan G protein-coupled receptor (SLC-1/GPR24) has been identified as a receptor for MCH (MCHR1). MCHR2 has higher protein sequence homology to MCHR1 than any other G protein-coupled receptor. MCHR2 is specifically activated by nanomolar concentrations of MCH, binds to MCH with high affinity, and signals through Gq protein[1].
Melanin Concentrating Hormone stimulates appetite. Continuous infusion of Melanin Concentrating Hormone into the ventricular system increases food intake for 7-8 days[2]. Intracerebroventricular infusion of Melanin Concentrating Hormone (10 μg/day) causes a slight but significant increase in body weight in mice maintained on the regular diet. Chronic stimulation of the brain Melanin Concentrating Hormone system could cause obesity in mice[3].
[1]. An S, et al. Identification and characterization of a melanin-concentrating hormone receptor. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7576-81. [2]. Della-Zuana O, et al. Acute and chronic administration of melanin-concentrating hormone enhances food intake and body weight in Wistar and Sprague-Dawley rats. Int J Obes Relat Metab Disord. 2002 Oct;26(10):1289-95. [3]. Gomori A, et al. Chronic intracerebroventricular infusion of MCH causes obesity in mice. Melanin-concentrating hormone. Am J Physiol Endocrinol Metab. 2003 Mar;284(3):E583-8. Epub 2002 Nov 26.
Cas No. | 87218-84-6 | SDF | |
别名 | 黑色素聚集激素肽,MCH (salmon) | ||
Canonical SMILES | Asp-Thr-Met-Arg-Cys-Met-Val-Gly-Arg-Val-Tyr-Arg-Pro-Cys-Trp-Glu-Val (Disulfide bridge: Cys5-Cys14) | ||
分子式 | C89H139N27O24S4 | 分子量 | 2099.48 |
溶解度 | DMSO : 100 mg/mL (47.63 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
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Characterization and expression of melanin-concentrating hormone (MCH) in common carp (Cyprinus carpio) during fasting and reproductive cycle
Melanin-concentrating hormone (MCH) was initially known as a regulator of teleost skin color and possesses multiple functions in mammals, such as the regulation of energy balance and reproduction. However, the role of MCH in fish remains unclear. In the present study, a 590 bp cDNA fragment of common carp (Cyprinus carpio) MCH gene was cloned. Amino acid sequence similarities with other teleost ranged from 23 to 93%. The mature MCH peptide (DTMRCMVGRVYRPCWEV) located in the C-terminal region of MCH precursor was 100% identical to that of goldfish, zebrafish, chum salmon, and rainbow trout. Tissue expression profiles showed that MCH mRNA was ubiquitously expressed throughout the brain and peripheral tissues and highly expressed in the brain and pituitary. Within the brain, MCH mRNA was expressed preponderantly in the hypothalamus. MCH mRNA expression in the hypothalamus was increased after feeding, decreased after 3, 5, or 7 days fasting, and increased upon refeeding. These results suggested that MCH might have anorexigenic actions in common carp. Meanwhile, MCH gene expression varied based on reproductive cycle, which might be related to the long-term regulation of MCH in energy balance. In conclusion, our novel finding revealed that MCH was involved in the regulation of appetite and energy balance in common carp.
The melanin-concentrating hormone: from the peptide to the gene
Melanin-concentrating hormone (MCH) is a cyclic peptide originally isolated from chum salmon pituitaries, then structurally characterized from rat hypothalami. In the fish, MCH induces melanin concentration within the melanophores and may inhibit ACTH secretion in vitro and under stressful conditions in vivo. In the rat, MCH modulates ACTH release in vivo and oxytocin secretion in vitro. However, on the basis of neuroanatomical features, that is, cell bodies almost exclusively confined to the lateral area of the hypothalamus and the zona incerta, while fibers are observed throughout whole rat or human brains, this peptide appears to participate as a neurotransmitter/neuromodulator in the control of goal-oriented behaviors and/or general arousal in mammals. The knowledge of structural and regulatory features of the MCH precursor, mRNA, and genes at the cellular and molecular levels has recently made great progress. (1) The cells expressing MCH and associated peptides have been defined conjointly using radioimmunoassay, immunocytochemistry, and in vitro and in vivo molecular hybridization techniques. (2) The organization of the precursor deduced from cDNA cloning has been established and led to the discovery of two novel putative peptides named NEI and NGE. (3) The regulation of MCH mRNA and peptide production has been explored during the course of development in rodent and human and under a variety of paradigms (neurogenic or osmotic stress, hormonal stimuli, etc.). (4) The structure of the MCH genes has been determined in salmon, rat, mouse, and human and revealed striking exon-intron organization differences between fish and mammals. Strong homology, with a likely functional implication, was found between salmon MCH mRNA and 7SL RNA, a structural RNA involved in protein translocation. Furthermore, a variant gene that may encode slightly different MCH was found exclusively in primates. (5) Chromosomal assignment of the authentic and variant MCH genes in rat and human indicates that these genes may be good candidates involved in neurodegenerative or psychiatric disorders. Based on the framework of these studies, a working model of MCH regulation/function in mammalian brain is finally proposed.
The melanin-concentrating hormone system and its physiological functions
Melanin-concentrating hormone (MCH) is a neuropeptide that was originally isolated from salmon pituitary where it causes pigment aggregation. MCH is also abundantly present in mammalian neurons and expressed in the lateral hypothalamus and zona incerta, brain regions that are known to be at the center of feeding behavior. MCH binds to and activates two G protein-coupled receptors, MCH1R and MCH2R. Although MCH2R is non-functional in rodents, genetic and pharmacological studies have demonstrated that rodent MCH1R is involved in the regulation of feeding behavior and energy balance. Unexpectedly, some antagonists have provided evidence that MCH signaling participates in the regulation of other processes, such as emotion and stress. The discovery of MCH receptors has extensively promoted the progress of MCH studies and may represent an ideal example of how deorphanized receptors can open new directions toward more detailed physiological studies.
Distribution of melanin-concentrating hormone (MCH)-like immunoreactivity in neurons of the diencephalon of sheep
An immunohistochemical study with an antiserum raised against salmon melanin concentrating-hormone has demonstrated the presence of numerous melanin concentrating-hormone-immunoreactive neurons in the lateral hypothalamic areas of the sheep. The pattern of distribution of these perikarya is similar to that of rodents and primates. In sheep, however, melanin concentrating-hormone-immunoreactive neurons appeared to form two gatherings: the first is situated ventromedially to the internal capsule and the second in the dorsolateral hypothalamus. In these areas, numerous immunostained perikarya are observed. Compared to the rats, labelled neurons extended more caudally in the ventral tegmental area and more rostrally above the optic chiasma. Compared to primates, these neurons are less numerous in the periventricular area. In our study, dense networks of melanin concentrating-hormone-immunoreactive varicose fibers were observed in the supramamillary nucleus, the lateral hypothalamus, the nucleus medialis thalami and nucleus reuniens and in the bed nucleus of the stria terminalis.
Melanin concentrating hormone. II. Structure and biosynthesis of melanin-concentrating hormone
Melanin-concentrating hormone is a neuropeptide produced in teleost hypothalami and transferred to the neurohypophysis. Salmon MCH was a novel cyclic heptadecapeptide capable of inducing melanin aggregation of integumentary melanophores at picoto nano-molar concentrations in all teleosts tested. The MCH gene is intronless and the exon encodes a 132 amino acid precursor protein, in which the heptadecapeptide of MCH locates at the C-terminal end. Immunohistochemical surveys with anti-salmon MCH antiserum strongly suggest that an MCH-like peptide is present in the hypothalami of higher vertebrates. Biological effects of salmon MCH on other vertebrates are found to be versatile.