MCHR2 Membrane Protein Introduction

Introduction of MCHR2

MCHR2 (Melanin-concentrating hormone receptor 2), referred to GPR145 (G-protein coupled receptor 145), is a G protein-coupled receptor protein present in humans encoded by the MCHR2 gene. As a receptor for melanin-concentrating hormone, MCHR2 enables to couple with G proteins and activates phosphoinositide hydrolysis. MCHR2 also exists in other species including dogs, ferrets, and some other primates and carnivores. However, MCHR2 is not found in mice or rats that are utilized in most early pharmaceutical research, which has delayed research into the receptor as a therapeutic target. As a neuropeptide, MCHR2 plays an essential role in the control of appetite regulation and energy metabolism.

Function of MCHR2 Membrane Protein

MCHR2 membrane protein is specifically present in the brain, where MCHR2 is expressed with the highest levels in cerebral cortex, hippocampus and amygdala, but not expressed in the cerebellum, thalamus or hypothalamus. MCHR2 together with GPR24, expressed in the human brain and other tissues, enable to be bound and activated by melanin-concentrating hormone (MCH) which is a conserved cyclic neuropeptide involved in the modulation of food intake. It has been suggested that the MCH-MCHR1 system plays a part in the regulation of feeding, emotional processing, and sleep in rodents. Recent research revealed that MCHR1 is selectively expressed in neuronal primary cilia of the central nervous system and may modulate the sensitivity of cells to external environments by controlling the cilia length.

Fig.1 Structure of MCHR2 membrane protein.

Application of MCHR2 Membrane Protein in Literature

1. Chee M.J., et al. Expression of melanin-concentrating hormone receptor 2 protects against diet-induced obesity in male mice. Endocrinology. 2014, 155(1): 81-88. PubMed ID: 24169555
   
   

   This article establishes an experimental animal model to provide insight into the action of MCHR2 in the central nervous system. The results suggest that some actions of MCHR2 oppose the endogenous actions of MCHR1.

2. Fried S., et al. Cloning and characterization of rhesus monkey MCH-R1 and MCH-R2. Peptides. 2002, 23(8):1401-8. PubMed ID: 12182940
   
   

   This article reveals that MCH binds to the monkey MCH-R1 receptor and the monkey MCH-R2 with a K(d) value similar to human MCH-R1 and MCH-R2. In addition, monkey MCH-R1 couples through G(i)/G(o) and G(q)-type G proteins similar to human MCH-R1 whereas monkey and human MCH-R2 utilizes the G(q) signaling pathway.

3. Tan C.P., et al. Melanin-Concentrating Hormone Receptor Subtypes 1 and 2: Species-Specific Gene Expression. Genomics. 2002, 79(6): 785-92. PubMed ID: 12036292
   
   

   This article demonstrates that no functional MCHR2 receptors exist, or a nonfunctional MCHR2 pseudogene encoded while retaining GPR24 expression in several non-human species (rat, mouse, hamster, guinea pig, and rabbit). Authors cloned and functionally characterized dog, ferret, and rhesus GPR24 and MCHR2 in mammalian cells and studied their brain distribution patterns by in situ hybridization.

4. Wang S., et al. Identification and pharmacological characterization of a novel human melanin-concentrating hormone receptor, mch-r2. J Biol Chem. 2001, 276 (37): 34664–70. PubMed ID: 11459838
   
   

   This article reports that the involvement of MCH-R2 plays a role in the central regulation of MCH-mediated functions.

5. Saito Y., et al. Molecular characterization of the melanin-concentrating-hormone receptor. Nature. 1999, 400(6741): 265-9. PubMed ID: 10421368
   
   

   Authors have analyzed the tissue localization of the MCH receptor and find that it is expressed in several brain regions, in particular those involved in olfactory learning and reinforcement mechanisms. The article has indicated that the MCH receptor is a potential therapeutic target for the neuronal regulation of food consumption.

MCHR2 Preparation Options

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