Melanocortin Receptor
Melanocortins, primarily consisting of a-melanocyte stimulating hormone (MSH), bMSH, g-MSH, and adrenocorticotropin (ACTH), are small peptide hormones derived from tissue-specific post-translational processing of a pre-prohormone, proopiomelanocortin(POMC). Functions of melanocortins on pigmentation and adrenal steroidogenesis are mediated by cell surface receptors that are coupled to the stimulatory heterotrimeric G protein, Gs. With the cloning of the classical MSH receptor and ACTH receptor, it was soon realized that three additional G protein-coupled receptors (GPCRs) with significant homology to the MSH receptor and ACTH receptor exist in mammalian genomes. The five cell-surface GPCRs that mediate melanocortin action are named MC1R (MSH receptor), MC2R (ACTH receptor), MC3R to MC5R, based on the sequence of their cloning. All five MCRs are coupled to the stimulatory G protein, increasing intracellular cAMP levels when the receptors are activated. MCRs also activate other signaling pathways, especially MAPKs, as shown extensively in other GPCRs. When the signaling in the canonical Gs-cAMP and non-canonical pathways are compared, differential response is observed in some instances. For example, the endogenous antagonist AgRP, while decreasing cAMP generation, stimulates ERK1/2 phosphorylation, therefore serving as agonist in the ERK1/2 pathway in both MC3R and MC4R.
References
1.Tao YX. Biochim Biophys Acta Mol Basis Dis. 2017;1863(10 Pt A):2411–2413.
References
1.Tao YX. Biochim Biophys Acta Mol Basis Dis. 2017;1863(10 Pt A):2411–2413.
GPCR/G Protein
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Leukotriene Receptor(9)
LHR(1)
LPA Receptor(12)
Lysophospholipid Receptor(13)
mAChR(25)
MCHR(6)
Melanocortin Receptor(22)
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SGLT(22)
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Melanocortin Receptor
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HS 014
catalog no : M30664
cas no: 207678-81-7
Potent and selective melanocortin MC4 receptor antagonist (Ki values are 3.16, 108, 54.4 and 694 nM for cloned human MC4, MC1, MC3 and MC5 receptors respectively). Increases food intake in rats and nociception in mice following central administration in vivo. Also inhibits IL-1β-induced Fos expression in the paraventricular hypothalamus. -
JKC 363
catalog no : M30660
cas no: 436083-30-6
Potent and selective melanocortin MC4 receptor antagonist (IC50 values are 0.5 and 44.9 nM at MC4 and MC3 respectively) that antagonizes the effects of α-MSH. Suppresses thyrotropin-releasing hormone (TRH) release, attenuates food intake and reduces formalin-induced pain in vivo. -
[D-Trp8]-γ-MSH
catalog no : M30647
cas no: 321351-81-9
Selective melanocortin 3 (MC3) receptor agonist (IC50 values are 6.7, 340 and 600 nM for human MC3, MC5 and MC4 receptors respectively). Displays anti-inflammatory efficacy. -
γ1-MSH
catalog no : M30646
cas no: 72629-65-3
Endogenous melanocortin MC3 receptor agonist (pKi = 7.46) that displays ~ 40-fold selectivity over MC4. Increases the release of extracellular dopamine, which induces grooming and vertical activity (rearing) in rats. Exhibits hypertensive, tachycardic and short-term analgesic activity in vivo. -
MSG 606
catalog no : M30645
cas no: 1416983-77-1
Potent human MC1 receptor antagonist (IC50 = 17 nM). Also partial agonist at human MC3 and MC5 receptors (EC50 values are 59 and 1300 nM, respectively). Exhibits binding affinity for A375 melanoma cells in vitro. Reverses morphine-induced hyperalgesia in female mice, with no effect in male mice. γMSH analog.