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Mice lacking Melanin-Concentrating Hormone are hypophagic and lean.
Shimada, M. et al., Nature 396, 670-673 (1998)

	4X  40X  Slides courtesy Dr. Nae Dun, James H. Quillen College of Medicine    East Tennessee State University

 Melanin Concentrating Hormone (MCH) related products


MELANIN-CONCENTRATING HORMONE RECEPTOR 2 (MCH-2R)

MCHR2 is a G protein-coupled receptor for MCH, a neuropeptide that plays an important role in the control of feeding behaviors and energy metabolism.

Melanin-concentrating hormone (MCH) is a cyclic neuropeptide originally isolated from the salmon pituitary gland. It regulates skin color in teleost fish in the induction of melanin aggregation in the melanocytes. Mammalian MCH is present in neurons of both the central and peripheral nervous systems, with predominant expression in the lateral hypothalamus and zona incerta. Its central role is in the control of feeding behaviors and energy metabolism. When administered centrally, MCH promotes food intake. Its expression in the lateral hypothalamus is induced by starvation. MCH knockout mice are lean and hypophagic and have increased metabolic rates and reduced body weight. Overexpression of MCH in transgenic mice leads to obesity. MCH and components of MCH signaling pathways are therefore very attractive as potential antiobesity drug targets. An and co-workers. (2001) identified MCHR2 by searching human genomic sequences with a GPCR (G protein-coupled receptor) hidden Markov model. They found that MCHR2 is most similar to MCHR1, with 36% amino acid identity overall and 44% amino acid identity in the transmembrane regions. The expression of MCHR2 was detected in most regions of the brain examined by RNA dot array hybridization. While MCHR1 is intronless in the coding region, the MCHR2 gene has 5 coding and 1 noncoding exon. MCHR2 is specifically activated by nanomolar concentrations of MCH, binds to MCH with high affinity, and signals through Gq protein.

Sailer and co-workers. (2001) simultaneously reported the identification of MCHR2 and likewise showed that it shares about 38% amino acid identity with MCHR1. They found that in contrast to MCHR1, MCHR2 signaling was not sensitive to pertussis toxin and MCHR2 cannot reduce forskolin-stimulated cAMP production, suggesting an exclusive G-alpha-q coupling of the MCHR2 in cell-based systems. By Northern blot and in situ hybridization analysis of human and monkey tissue, Sailer and co-workers (2001) showed that expression of MCHR2 mRNA is restricted to several regions of the brain, including the arcuate nucleus and the ventral medial hypothalamus, areas implicated in regulation of body weight.

Holder and co-workers (2000) described an obese girl with a balanced translocation involving the region of chromosome 6 where the MCHR2 resides; they demonstrated disruption of the SIM1 gene located at 6q16.2. Sailer and co-workers (2001) estimated that the SIM1 and MCHR2 genes are located within 1 Mb of each other. As reviewed by Gilhuis and co-workers (2000), 4 other obese patients with cytogenetic alterations in the same region of 6q had been reported; all had in common some clinical features, including obesity, hypotonia, and developmental delays, resembling Prader-Willi syndrome (PWS). However, their behavior, facial features, and additional neurologic abnormalities, as well as a lack of cytogenetic changes or imprinting mutations on chromosome 15, clearly distinguished this PWS-like phenotype from PWS patients.

MCH-2R Antibody for Immunohistochemistry

Human MCH-R2 Immunohistochemistry Protocol

MCH-R2 Immunohistochemistry Tissue Sample Rat brain Fixative 10% formalin Embedding paraffin Negative Control No primary antibody Pretreatment Target retrieval 25 min (Steam) Blocking 2% Normal Goat Serum Primary Antibody Anti-MCH-R2 (237-259), Cys0,(Human) Antibody (Catalog No.: H-071-20) Optimal Dilution 1:100 Secondary Antibody Goat Anti-Rabbit IgG, Biotinylated (1:400) Amplification ABC (Vector) Detection System HRP Substrate DAB (Sigma) Counterstained Hematoxylin

New Anti-MCH-2R (237-251), Cys0,(Human) Antibody Detection of MCH-2R with dot blot analysis

References: Sailer, A. W.; Sano, H.; Zeng, Z.; McDonald, T. P.; Pan, J.; Pong, S.-S.; Feighner, S. D.; Tan, C. P.; Fukami, T.; Iwaasa, H.; Hreniuk, D. L.; Morin, N. R.; and 15 others : Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R. Proc. Nat. Acad. Sci. 98: 7564-7569, 2001. An, S.; Cutler, G.; Zhao, J. J.; Huang, S.-G.; Tian, H.; Li, W.; Liang, L.; Rich, M.; Bakleh, A.; Du, J.; Chen, J.-L.; Dai, K. : Identification and characterization of a melanin-concentrating hormone receptor. Proc. Nat. Acad. Sci. 98: 7576-7581, 2001. Hill, J.; Duckworth, M.; Murdock, P.; Rennie, G.; Sabido-David, C.; Ames, R. S.; Szekeres, P.; Wilson, S.; Bergsma, D. J.; Gloger, I. S.; Levy, D. S.; Chambers, J. K.; Muir, A. I. : Molecular cloning and functional characterization of MCH-2, a novel human MCH receptor. J. Biol. Chem. 276: 20125-20129, 2001. Mori, M.; Harada, M.; Terao, Y.; Sugo, T.; Watanabe, T.; Shimomura, Y.; Abe, M.; Shintani, Y.; Onda, H.; Nishimura, O.; Fujino, M. : Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor. Biochem. Biophys. Res. Commun. 283: 1013-1018, 2001. Holder, J. L.; Jr.; Butte, N. F.; Zinn, A. R. : Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum. Molec. Genet. 9: 101-108, 2000. Gilhuis, H. J.; van Ravenswaaij, C. M.; Hamel, B. J. C.; Gabreels, F. J. M. : Interstitial 6q deletion with a Prader-Willi-like phenotype: a new case and review of the literature. Europ. J. Paediat. Neurol. 4: 39-43, 2000. McKusick, V. A. et al.OMIM:*606111

Amino Acid Sequence of MCH-R2 (Human)    1 mnpfhascwn tsaellnksw nkefayqtas vvdtvilpsm igiicstglv gnilivftii  61 rsrkktvpdi yicnlavadl vhivgmpfli hqwarggewv fggplctiit sldtcnqfac 121 saimtvmsvd ryfalvqpfr ltrwrtrykt irinlglwaa sfilalpvwv yskvikfkdg 181 vescafdlts pddvlwytly ltittfffpl plilvcyili lcytwemyqq nkdarccnps 241 vpkqrvmklt kmvlvlvvvf ilsaapyhvi qlvnlqmeqp tlafyvgyyl siclsyasss 301 inpflyills gnfqkrlpqi qrratekein nmgntlkshf   Product Name Code Quantity Price MCH-R2 (237-251) , Cys0,(Human) Antibody H-071-20 50ul $450 MCH-R2 (237-251), Cys0, (Human)  Purified IgG G-071-20 200ug $450 MCH-R2 (237-251) , Cys0,(Human) Purified IgG FAM labeled FG-G-071-20 100ul $500 MCH-R2 (237-251) , Cys0, (Human) Purified IgG Rhodamine labeled FR-G-071-20 100ul $500 MCH-R2 (237-251) , Cys0, (Human) Purified IgG Biotin labeled B-G-071-20 100ul $500 MCH-R2 (237-251) (Human) Dot Blot Kit DBK-071-20 kit $650 MCH-R2 (237-251) (Human) 071-20 100ug $140

Comparison of half-maximal concentrations for binding at and functional activation of human MCH-1R and MCH-2R by MCH, Phe13Tyr19-MCH, and salmon MCH   Ligand Binding IC50, nM ± SEM (n) Function EC50, nM ± SEM (n) MCH-1R MCH-2R MCH-1R MCH-2R   MCH 0.3  ± 0.1 (10) 1.5  ± 0.9 (8) 3.9  ± 1.2 (3) 0.1  ± 0.1 (3) Phe13Tyr19-MCH 0.3  ± 0.1 (3) 0.8  ± 0.1 (3) 8.5  ± 0.9 (3) 0.2  ± 0.1 (3) Salmon MCH 0.2  ± 0.1 (5) 436.7  ± 143.8 (3) 35.0  ± 14.8 (3) 0.8  ± 0.1 (3)   Membrane binding was assessed by competition of [125I]Phe13Tyr19-MCH in a scintillation proximity assay. Functional activation was measured by mobilization of intracellular calcium detected in a fluorometric imaging plate reader assay. Values shown are nanomolar concentrations and averaged from at least three independent experiments. Fig. (A) Agonist-induced calcium mobilization in a CHO cell line stably expressing human MCH-2R as detected by a fluorometric imaging plate reader (FLIPR) assay. MCH, Phe13Tyr19-MCH , salmon MCH;(B) Membrane binding assay using a scintillation proximity assay measuring specific binding of [125I]Phe13Tyr19-MCH to MCH-2R containing membranes. (C and D) PTX sensitivity of intracellular calcium mobilization mediated by MCH-1R (C) or MCH-2R (D) in HEK293-AEQ17 cell lines. Stable transfected HEK293-AEQ17 cell lines were treated with 0 ng/ml (circles), 150 ng/ml (triangles), 500 ng/ml (diamonds), or 5,000 ng/ml (rectangles) PTX before the aequorin assay. Sailer AW, et al. Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R. Proc Natl Acad Sci U S A 2001 Jun 19;98(13):7564-9

Recently, two groups have identified a 353 amino acid G-coupled orphan receptor as receptor for MCH: Chambers, J. et al., Nature 400, 261-265 (1999) and Saito, Y. et al., Nature 400, 265-269 (1999). We offer several rat SLC-1 receptor fragments for antibody production as well as MCH and related peptides for obesity research and other studies.


 Melanin Concentrating Hormone (MCH) related products

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