Melanin-Concentrating Hormone GPCR Assays
Introduction to Melanin-Concentrating Hormone Receptors
Melanin-concentrating hormone receptor (MCHR) is one of the G-protein coupled receptors (GPCRs) characterized to bind melanin-concentrating hormone (MCH), a cyclic 19-amino acid neuropeptide with a major role in feeding behaviors and energy metabolism. MCHR consists of two members, MCHR1 and MCHR2, both of which exhibit high affinity to MCH peptides and share 38% homology. MCHR1, previously known as SLC1 or GPR24, is highly expressed in brain areas of all mammals, rodents, and primates. While, MCHR2 (GPR145) was later identified in humans that only detected in fishes, dogs, ferrets, and some non-human primates.
Fig.1 Structure of MCH and MCHR1. (Philippe, 2017)
Expression and Functions of Melanin-Concentrating Hormone Receptors
In mammals, both MCHR1 and MCHR2 are dominantly expressed in the brain. MCHR1 is widely distributed in many areas of the brain, such as the cortex, hippocampus, basal ganglia, hypothalamus, thalamus, midbrain, etc., suggesting its wide range of functions in the regulation of behaviors, emotions, appetite, and memories. MCHR1 also has distribution in peripheral tissues, such as adipose tissue, lymphocytes, and intestine, which may be implicated with energy balance and metabolism. MCHR2 has a similar distribution to MCHR1 with a more limited expression in the limbic regions. The research progress was hampered since it was not expressed in rodents.
Fig.2 Signaling pathways of MCHR1 and MCHR2. (Bencze, 2018)
Mechanisms of Melanin-Concentrating Hormone Receptors
The MCHR1 affects cell proliferation and gene transcription through the activation and cascade of G proteins. Usually, MCHR1 and MCHR2 bind to their ligand MCH with high affinity and couple to G protein to activate the intracellular signaling pathways. The activation of the Gi protein leads to the decrease of adenylate cyclase activity, causing a reduction of cAMP and protein kinase C (PKA). The activation of the Gq protein can increase the activity of mitogen-activated protein kinase (MAPK) through the Ras activation and inositol trisphosphate (IP3)-mediated Ca2+ elevation. Both PKA and MAPK are important regulators of gene transcription and cell proliferation.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| MCHR1 | MCHR1 |
|
|
|
| MCHR2 | MCHR2 |
|
|
Assay List of Melanin-concentrating Hormone Receptors
Creative Biolabs can provide a range of assays of melanin-concentrating hormone receptors. You can choose the assay in the list or contact us for more information:
| Assay No. | Assay Name | Host Cell | Assay Type | Datasheet |
|---|---|---|---|---|
| Calcium Flux Assay | ||||
| S01YF-0722-KX130 | Magic™ Human MCHR2 In Vitro Calcium Assay, HEK293 | HEK293 | Calcium Flux Assay | |
Published Data
| Paper Title | Determination of the Interaction and Pharmacological Modulation of MCHR1 Signaling by the C-Terminus of MRAP2 Protein |
| Journal | Frontiers in Endocrinology |
| Published | 2022 |
| Abstract | MCHR1, together with several other GPCRs, has been demonstrated to interact with melanocortin receptor accessory protein 2 (MRAP2), exerting an important regulatory action in central and peripheral biological processes. Here, researchers have evaluated the interaction between MRAP2 and MCHR1 through several assays. |
| Result |
Enzyme-linked immunosorbent assay, confocal microscopy, and sequence analysis have indicated that MRAP2 interacted with MCHR1, remarkably inhibited the MCHR1 expression, and the interaction could be blocked by deletion of the whole C-tail MRAP2.
|
Fig.3. Regulation of MCHR1 trafficking by WT MRAP2 and its mutants. (Wang, 2022)
References
- Philippe, C., and Mitterhauser, M. The Potential Role of the MCHR1 in Diagnostic Imaging: Facts and Trends. 2017, In (Ed.), Melanin. IntechOpen. https://doi.org/10.5772/67185
- Bencze, J.; et al. The melanin-concentrating hormone system in human, rodent and avian brain. Open Medicine. 2018, 13(1): 264-269.
- Wang, M.; et al. Determination of the Interaction and Pharmacological Modulation of MCHR1 Signaling by the C-Terminus of MRAP2 Protein. Frontiers in Endocrinology. 2022, 13: 848728.
