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Targeting melanocortin receptors as a novel strategy to control inflammation

Catania A, Gatti S, Colombo G +1 more2004Pharmacological ReviewsReview
10.1124/pr.56.1.1PubMed
CardiovascularEndocrine (ADH/ACTH/MSH)GastrointestinalHypothalamic-PituitaryImmune/InnateMusculoskeletalNeurologicalOcularRespiratory/Sinus
ActinomycetesBacterial EndotoxinsIndoor Mold (Stachybotrys, Aspergillus, etc.)MycotoxinsVolatile Organic Compounds (VOCs)Water-Damaged Buildings (WDB)

Abstract

Adrenocorticotropic hormone and alpha-, beta-, and gamma-melanocyte-stimulating hormones, collectively called melanocortin peptides, exert multiple effects upon the host. These effects range from modulation of fever and inflammation to control of food intake, autonomic functions, and exocrine secretions. Recognition and cloning of five melanocortin receptors (MCRs) has greatly improved understanding of peptide-target cell interactions. Preclinical investigations indicate that activation of certain MCR subtypes, primarily MC1R and MC3R, could be a novel strategy to control inflammatory disorders. As a consequence of reduced translocation of the nuclear factor kappaB to the nucleus, MCR activation causes a collective reduction of the major molecules involved in the inflammatory process. Therefore, anti-inflammatory influences are broad and are not restricted to a specific mediator. Short half-life and lack of selectivity could be an obstacle to the use of the natural melanocortins. However, design and synthesis of new MCR ligands with selective chemical properties are already in progress. This review examines how marshaling MCR could control inflammation.

Key Biomarkers

Alpha Melanocyte Stimulating Hormone (MSH)Immunoglobulin E (IgE)LeptinMatrix Metalloproteinase 9 (MMP9)Vascular Endothelial Growth Factor (VEGF)Visual Contrast Sensitivity (VCS)

Symptom Clusters

Autonomic/endocrine symptoms (excessive thirst, frequent urination, night sweats, mood swings, appetite swings)Constitutional symptoms (fatigue, headache)Multiple organ system involvementMusculoskeletal symptoms (muscle aches, joint pain, ice pick pain)Neurological pain (tingling in extremities, chronic pain)Neurological symptoms (memory loss, concentration difficulty, confusion, word-finding difficulty)Pulmonary symptoms (cough, shortness of breath)Upper respiratory/sinus symptomsVisual dysfunction (light sensitivity, abnormal visual contrast sensitivity)

Cited By (25)

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  • Inhibitory effects of the peptide (CKPV)2 on endotoxin-induced host reactionsJournal of Surgical Research · 2006
  • PRODUCTION AND EFFECTS OF α-MELANOCYTE-STIMULATING HORMONE DURING ACUTE LUNG INJURYShock · 2007
  • Alpha-melanocyte-stimulating hormone contributes to an anti-inflammatory response to lipopolysaccharideMolecular Metabolism · 2024
  • Activation of Melanocortin 4 Receptors Reduces the Inflammatory Response and Prevents Apoptosis Induced by Lipopolysaccharide and Interferon-γ in AstrocytesEndocrinology · 2007
  • Immunomodulatory Role of Neuropeptides in the Cornea

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