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Melanin-concentrating hormone (MCH) was initially discovered in the pituitary glands of salmon and then studied in the hypothalamus of rats. Afterwards, MCH was established in numerous mammalian species, including humans, in the brain and periphery. MCH mRNA and peptide syntheses were primarily identified in neurons that propagated from the lateral hypothalamus and zona incerta across the central nervous system and the brain. A wide range of functions were demonstrated by the central MCH, with an important part being performed in energy maintenance by reducing energy expenditure and promoting eating behavior. There are two high-affinity MCH receptors known.

The structure of mammalian MCH.Fig.1 The structure of mammalian MCH.1,2

Creative Biolabs offers high-quality melanin-concentrating hormone family in vitro assays and products to contribute to the success of your project:

Overview of Melanin-concentrating Hormone Family

MCH, a natural ligand, binds to MCHR1 and couples to the proteins Gi, Go, and Gq. Hence, activation of MCHR1 results in increased intracellular Ca2+ accumulation via the Gq-coupled pathway and decreased levels of cyclic adenosine monophosphate (cAMP) via the Gi/o-coupled pathway. Further research on the MCHR1 signaling in recombinant cell lines and in brain slices shows that MCHR1 activation also results in ERK phosphorylation. MCH quickly generated a three- to fivefold increase in MAPK pathway activity in 3T3-L1 adipocytes.

A second MCHR was discovered and given the name MCHR2. With only 38% amino acid identity between MCHR1 and MCHR2, the seven transmembrane domains that make up the ligand binding pocket have the most homology. Although MCH has a similar nanomolar affinity for both MCHR1 and MCHR2, MCHR2's signal transduction mechanism is only the Gq-mediated elevation of intracellular Ca2+ levels. Although peripheral expression was also discovered in adipocytes, the pancreas, the prostate, and the intestine, MCHR2 and MCHR1 are mostly co-expressed in the CNS. Opioid, somatostatin, galanin, urotensin 2, and orphan receptors can be found on the evolutionary tree of MCH-related receptors. The most similar receptors to somatostatin receptors are MCH receptors.

Melanin-concentrating Hormone Family Drug Discovery

Many businesses have experimented with a range of non-peptide MCH antagonists that target MCH-R1. As a result, the chemicals are touted as having applications in the treatment or prevention of a variety of illnesses, including diabetes, hyperlipidemia, depression, anxiety, and associated physical symptoms, as well as neurodegenerative and mental disorders. There is no doubt that viable candidates will be found among this enormous number of chemicals and then be submitted to clinical trials. Nonetheless, significant uncertainties still exist regarding the function of MCH and MCH-R1 in the regulation of energy balance and other behaviors. Also, comprehensive research and the creation of appropriate animal models are necessary for the MCH physiological functions in the human brain that are mediated by MCH-R2.

References

  1. MacNeil, Douglas J. "The role of melanin-concentrating hormone and its receptors in energy homeostasis." Frontiers in endocrinology 4 (2013): 49.
  2. Distributed under Open Access License CC BY 4.0. The original image was modified by extracting and changed the color and the title was changed to " The structure of mammalian MCH.".

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