Trends in Pharmacological Sciences
Research updateMelanocortin peptides and their receptors: new targets for anti-inflammatory therapy
Section snippets
Melanocortins and inflammation
α-MSH has long been reported to be active in models of allergic and chronic inflammation, potently suppressing oedema formation and inhibiting leukocyte migration. Some α-MSH actions might be due to the C-terminal tripeptide KPV that corresponds to α-MSH11–13 (Fig. 1b). For example, the KPV tri-peptide antagonizes the binding of interleukin 1β (IL-1β) to its receptor, suggesting that α-MSH might also function as an IL-1 receptor antagonist [3]. This action might explain the anti-pyretic effect
Which melanocortin receptor modulates inflammation?
Two receptor candidates (MC3 and MC1) with different tissue distributions and levels of cellular expression have been proposed to be responsible for modulating the anti-inflammatory effects of melanocortin.
The MC1 receptor has long been regarded as the receptor responsible for the anti-inflammatory effects of α-MSH and related peptides [1]. Using flow cytometry, Anderson et al. found expression of MC1 receptor in monocytes, B cells, natural killer cells and a subset of cytoxic T cells, but not
Pharmacological effects of melanocortin peptides in other pathological models
Until recently, most studies have focused on the anti-inflammatory effects of melanocortin peptides in experimental models of acute and, to a lesser extent, chronic inflammation. Melanocortins have multiple biological actions; for example, they exert a protective effect in a rat model of myocardial infarct [17] and in models of endotoxin-induced colonic inflammation [18] and mesenteric ischaemia–reperfusion injury [19]. Other disease models have been shown to be susceptible to melanocortin
Concluding remarks
The role played by melanocortin peptides in modulating the host inflammatory response is beyond doubt. Along with many other anti-inflammatory substances these peptides play a protective role in maintaining the homeostatic balance within the body. The receptor type involved in modulating the inflammatory response has yet to be identified with certainty, although the availability of mice with non-functional MC1 receptors or the generation of knockout MC3 receptors [20] will help to address this
Chemical names
HS024 Ac-Cys-Nle-Arg-His-dNal(2′)-Arg-Trp-Gly-Cys-NH2 MTII Ac-Nle-c[Asp-His-dPhe-Arg-Trp-Lys]-NH2 SHU9119 Ac-Nle-c[Asp-His-dNal(2′)-Arg-Trp-Lys]-NH2
Acknowledgements
I would like to thank the Arthritis Research Campaign, UK (grant no. PO562) for their continued support.
References (20)
New aspects on the melanocortins and their receptors
Pharmacol Res.
(2000)Inhibition of peripheral NF-κB activation by central action of α-melanocyte-stimulating hormone
J. Neuroimmunol.
(1999)γ2-Melanocyte-stimulating hormone suppression of systemic inflammatory responses to endotoxin is associated with modulation of central autonomic and neuroendocrine activities
J. Neuroimmunol.
(2001)α-Melanocyte stimulating hormone acts as a selective inducer of secretory functions in human mast cells
Biochem. Biophys. Res. Commun.
(2000)The effect of α-melanocyte stimulating hormone on endotoxin-induced intestinal injury
Peptides
(2001)Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat
Nat. Neurosci.
(2001)- et al.
Arthritic diseases: melanocortin type 3 receptor agonists as potential therapeutics
Curr. Opin. Invest. Drugs
(2001) POMC gene-derived peptides activate melanocortin type 3 receptor on murine macrophages, suppress cytokine release and inhibit neutrophil migration in acute experimental inflammation
J. Immunol.
(1999)- et al.
Melanocyte stimulating hormone inhibits the nuclear transcription factor NF-kB activation by various inflammatory agents
J. Immunol.
(1998) Mechanisms of the anti-inflammatory effects of α-MSH. Role of transcription factor NF-κB and adhesion molecule expression
Ann. New York Acad. Sci.
(1999)
Cited by (65)
Memory impairment induced by IL-1β is reversed by α-MSH through central melanocortin-4 receptors
2009, Brain, Behavior, and ImmunityCitation Excerpt :This clear neuroprotective effect occurring at low doses is probably mediated by brain melanocortin MC4 receptors. Melanocortins are widely distributed in the CNS and MC4 receptors have been found in various brain areas including the hippocampus (Getting, 2002). Administration of HS014, a selective MC4R antagonist, reversed the effect of α-MSH on the impairment of memory consolidation induced by IL-1β suggesting that α-MSH may exert this effect by activating central MC4R.
Neuroprotection in focal cerebral ischemia owing to delayed treatment with melanocortins
2007, European Journal of PharmacologyGlial Cells Response in Stroke
2023, Cellular and Molecular Neurobiology