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Melanin Concentrating Hormone (MCH) and NEI-MCH [Prepro-MCH (132-165)]
Obesity Peptides
Mice lacking Melanin-Concentrating Hormone are hypophagic and lean.
Shimada, M. et al., Nature 396, 670-673 (1998)
MCH Receptor Ligand, SLC-1 (Rat) Orphan Receptor Fragments and Related Peptides
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.
Appetite-boosting property of pro-melanin-concentrating hormone(131-165) (neuropeptide-glutamic acid-isoleucine) is associated with proteolytic resistance
Melanin-concentrating hormone (MCH) is a cyclic neuropeptide, with a major role in stimulation of feeding behavior in mammals. MCH signals in the brain occur via two seven-transmembrane G protein-coupled receptors, namely MCH1 (SLC-1, MCH(1), MCH-R1, or MCH-1R) and MCH2 (SLT, MCH(2), MCH-R2, or MCH-2R). In this study, we demonstrate that the pro-MCH(131-165) peptide neuropeptide-glutamic acid-isoleucine (NEI)-MCH is more potent than MCH in stimulating feeding in the rat. Using rat MCH1-expressed human embryonic kidney 293 cells, we show that NEI-MCH exhibits 5-fold less affinity in a binding assay and 2-fold less potency in a cAMP assay than MCH. A similar 7- to 8-fold shift in potency was observed in a Ca(2+)(i) assay using rat MCH1 or human MCH2-transfected Chinese hamster ovary cell models. This demonstrates that NEI-MCH is not a better agonist than MCH at either of the MCH receptors. Then, we compared the proteolysis resistance of MCH and NEI-MCH to rat brain membrane homogenates and purified proteases. Kinetics of peptide degradation using brain extracts indicated a t(1/2) of 34.8 min for MCH and 78.5 min for NEI-MCH with a specific pattern of cleavage of MCH but not NEI-MCH by exo- and endo-proteases. Furthermore, MCH was found highly susceptible to degradation by aminopeptidase M and endopeptidase 24.11, whereas NEI-MCH was fully resistant to proteolysis by these enzymes. Therefore, our results strongly suggest that reduced susceptibility to proteases of NEI-MCH compared with MCH account for its enhanced activity in feeding behavior. NEI-MCH represents therefore the first MCH natural functional "superagonist" so far described. Maulon-Feraille L, J Pharmacol Exp Ther 2002 Aug;302(2):766-73
Melanin Concentrating Hormone (MCH) related products.
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