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Research ArticleArticle

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

Anna Catania, Stefano Gatti, Gualtiero Colombo and James M. Lipton
Pharmacological Reviews March 2004, 56 (1) 1-29; DOI: https://doi.org/10.1124/pr.56.1.1
Anna Catania
Divisions of Internal Medicine (A.C., G.C.) and Liver Transplantation (S.G.), Ospedale Maggiore di Milano, Istituto di Ricovero e Cura a Carattere Scientifico, Milano, Italy; and Zengen, Inc. (J.M.L.), Woodland Hills, California
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Stefano Gatti
Divisions of Internal Medicine (A.C., G.C.) and Liver Transplantation (S.G.), Ospedale Maggiore di Milano, Istituto di Ricovero e Cura a Carattere Scientifico, Milano, Italy; and Zengen, Inc. (J.M.L.), Woodland Hills, California
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Gualtiero Colombo
Divisions of Internal Medicine (A.C., G.C.) and Liver Transplantation (S.G.), Ospedale Maggiore di Milano, Istituto di Ricovero e Cura a Carattere Scientifico, Milano, Italy; and Zengen, Inc. (J.M.L.), Woodland Hills, California
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James M. Lipton
Divisions of Internal Medicine (A.C., G.C.) and Liver Transplantation (S.G.), Ospedale Maggiore di Milano, Istituto di Ricovero e Cura a Carattere Scientifico, Milano, Italy; and Zengen, Inc. (J.M.L.), Woodland Hills, California
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Abstract

Adrenocorticotropic hormone and α-, β-, and γ-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 κB 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.

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Pharmacological Reviews: 56 (1)
Pharmacological Reviews
Vol. 56, Issue 1
1 Mar 2004
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Research ArticleArticle

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

Anna Catania, Stefano Gatti, Gualtiero Colombo and James M. Lipton
Pharmacological Reviews March 1, 2004, 56 (1) 1-29; DOI: https://doi.org/10.1124/pr.56.1.1

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Research ArticleArticle

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

Anna Catania, Stefano Gatti, Gualtiero Colombo and James M. Lipton
Pharmacological Reviews March 1, 2004, 56 (1) 1-29; DOI: https://doi.org/10.1124/pr.56.1.1
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  • Article
    • Abstract
    • I. Introduction
    • II. Proopiomelanocortin Gene, Gene Expression, and Post-Translational Processing
    • III. Melanocortin Receptors and Their Endogenous Antagonists
    • IV. Intracellular Signaling
    • V. Structure-Activity Relationship of Melanocortin Peptides
    • VI. Mechanism of the Anti-Inflammatory Action of Melanocortins
    • VII. Antipyretic Influences of Melanocortins
    • VIII. Changes in Endogenous α-Melanocyte-Stimulating Hormone in Inflammatory Disorders
    • IX. Potential Therapeutic Targets Based on Preclinical Studies in Inflammatory Disorders
    • X. Advantages over Currently Used Anti-Inflammatory Drugs and Potential Disadvantages
    • Footnotes
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