The MC3 receptor binding affinity of melanocortins correlates with the nitric oxide production inhibition in mice brain inflammation model

Ruta Muceniece, Liga Zvejniece, Edgars Liepinsh, Olga Kirjanova, Larisa Baumane, Ramona Petrovska, Felikss Mutulis, Ilze Mutule, Ivars Kalvinsh, Jarl E.S. Wikberg, Maija Dambrova

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Melanocortins possess strong anti-inflammatory effects acting in the central nervous system via inhibition of the production of nitric oxide (NO) during brain inflammation. To shed more light into the role of melanocortin (MC) receptor subtypes involved we synthesized and evaluated some novel peptides, modified in the melanocyte-stimulating hormone (MSH) core structure, natural MCs and known MC receptor selective peptides - MS05, MS06. Since the study included both selective, high affinity binders and the novel peptides, it was possible to do the correlation analysis of binding activities and the NO induction-related anti-inflammatory effect of the peptides. β-MSH, γ1-MSH, γ2-MSH, α-MSH, MS05, Ac-MS06 and Ac-[Ser12]MS06 caused dose dependent inhibition of the lipopolysaccharide (LPS)-induced increase of NO overproduction in the mice forebrain whereas MSH core modified peptides Ac-[Asp9,Ser12]MS06, [Asp9]α-MSH and [Asp16]β-MSH were devoid of this effect in doses up to 10 nmol per mouse. When the minimal effective dose required for inhibition of NO production was correlated with the in vitro binding activity to MC receptor subtypes a strong and significant correlation was found for the MC3 receptor (r = 0.90; p = 0.0008), whereas weak correlation was present for the other receptors. Our results suggest that the MC3 receptor is the major player in mediating the anti-inflammatory activity of MCs in the central nervous system.

Original languageEnglish
Pages (from-to)1443-1450
Number of pages8
JournalPeptides
Volume27
Issue number6
DOIs
Publication statusPublished - Jun 2006
Externally publishedYes

Keywords*

  • Brain inflammation
  • MC receptors
  • Melanocortins
  • Nitric oxide

Field of Science*

  • 1.6 Biological sciences
  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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