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MCH Receptor Family

Melanin-concentrating hormone (MCH) receptors form a small part of GPCRs family, which can bind MCH, a 19-amino acid cyclic peptide encoded within a 165-amino acid preprohormone in mammalian. The distribution of MCH is general from fishes to mammals and it is not linked to pigmentation but seems to be essential in appetite regulation and obesity. Later on, a variety of physiologic processes mediated within the central nervous system (CNS), including energy homeostasis sleep and arousal, and emotionality are confirmed to be associated with MCH. Two MCH receptors (MCHR) have recently been characterized as MCHR1 and MCHR2, sharing approximately 38% homology. MCHR1 is expressed in all mammals, while MCHR2 is only found in some primates and carnivores including dogs, ferret, and humans. In higher species, the highest expressions of MCHR1 and MCHR2 are detected in the brain: frontal cortex, amygdala and nucleus accumbens, but also in the arcuate nucleus and in the ventral medial hypothalamus. These receptors are also moderately expressed in peripheral organs. The molecular pharmacology of MCHR1 and MCHR2 suggests that homologous antagonists might be useful in the treatment of obesity, anxiety and depression.

Here show two members of MCHRs: MCHR1 and MCHR2. MCHR2 displays a 10-fold less potent affinity for MCH than MCHR1. MCHR1 activation leads to an increase in intracellular Ca2+ accumulation acting through the Gq-coupled pathway and/or reduction of cyclic adenosine monophosphate (cAMP) levels via the Gi/o-coupled pathway. While the signal transduction mechanism of MCHR2 is limited to the Gq-mediated increase in intracellular Ca2+ levels.

Human MCHRs Members
MCHR1 MCHR2

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