Melanin-Concentrating Hormones (MCH) and Related Peptides

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Introduction

Melanin-concentrating hormone (MCH) is a cyclic 19-amino acid neuropeptide synthesized by neurons involved with homeostatic regulation and motivated behaviors. The MCH neurons are mainly located in the lateral hypothalamic (LHA) and incerto-hypothalamic (IHy) areas of rats, non-human primates and human. MCH-expressing LHA and IHy neurons also co-express the neuropeptide EI (NEI) and neuropeptide GE (NGE), two peptides clived from the same MCH pre-propeptide precursor (ppMCH).

Mechanism of action

The biological functions of MCH are mediated by two G-protein coupled receptors: MCHR1 and MCH2R. MCHR1 activation acts selectively through of Gαi/o and Gαq proteins, promoting the inhibition of adenylate cyclase, increased Ca²⁺ influx and activation of MAP kinase, which confer to MCHR1 activation a predominant inhibitory mode of action. However, MCHR2 mechanisms are still largely unknown. MCH acts as an important neuromodulator for the organism homeostatic balance, acting over a large spectrum of integrative functions, especially those related to homeostatic regulation and motivated behaviors. One of its best described function is to dampens energy expenditure, and to a lesser extend its orexigenic properties . There is, however, an increase in the number of physiological functions associated with it, including learning and memory, attention modulation, stress and anxiety, reproductive system modulation. A massing experimental evidence support a role for the MCH system in the sleep-wake state control.

Application of MCH and Related Peptide

MCH signaling is likely to be involved in a wide range of physiological functions, suggesting that MCH1R antagonists may be useful in many human disorders. The current scientific literature has shown that MCH1R antagonists are efficacious in animal models of depression, anxiety, sleep, and reward. The neuroanatomical and peripheral distribution of MCH1 receptors suggest that MCH is involved in more functions than are currently known. MCH1R antagonists will be invaluable tools for discovering additional functions of MCH signaling and will likely have therapeutic value in many disorders.

References

1. Jae-Hwan Jang., Ji-Yeun Park., Ju-Young Oh Sun-Jeong Bae., Hyunchul Jang., Songhee Jeon., Jongpil Kim., &Hi-Joon Park. (2018). Novel analgesic effects of melanin-concentrating hormone on persistent neuropathic and inflammatory pain in mice. Sci Rep, 8, 707.
2. Jozelia Gomes PachecoFerreira,. Jackson CioniBittencourt,. &Antoine Adamantidis. (2017). Melanin-concentrating hormone and sleep. Current Opinion in Neurobiology, 44, 152-158.
3. Shinjae Chung., Gregory S. Parks., Cheol Lee., &Olivier Civellicorresponding author. (2011). Recent Updates on the Melanin-Concentrating Hormone (MCH) and Its Receptor System: Lessons from MCH1R Antagonists. J Mol Neurosci, 43(1): 115-121.