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

6533b829fe1ef96bd1289a01

RESEARCH PRODUCT

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

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

subject

Central Nervous System Lipopolysaccharides Male medicine.medical_specialty Insecta Lipopolysaccharide Physiology Anti-Inflammatory Agents Inflammation Biology Nitric Oxide Biochemistry Nitric oxide Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Endocrinology Melanocortin receptor Internal medicine medicine Animals Receptor Melanocortins Inflammation Mice Inbred ICR integumentary system Receptors Melanocortin Electron Spin Resonance Spectroscopy Cell biology Endocrinology chemistry Forebrain medicine.symptom Melanocortin Peptides hormones hormone substitutes and hormone antagonists Protein Binding Receptor Melanocortin Type 3

description

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. beta-MSH, gamma1-MSH, gamma2-MSH, alpha-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]alpha-MSH and [Asp16]beta-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.

year	journal	country	edition	language
2006-06-01	Peptides

https://doi.org/10.1016/j.peptides.2005.12.002