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Natural and synthetic agonists of the melanocortin receptor type 3 possess anti-inflammatory properties

Getting, Stephen J. and Allcock, Graham H. and Flower, Roderick J. and Perretti, Mauro (2001) Natural and synthetic agonists of the melanocortin receptor type 3 possess anti-inflammatory properties. Journal of Leukocyte Biology, 69 (1). pp. 98-104. ISSN 0741-5400

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Abstract

The effects of the natural and synthetic ligands for the melanocortin receptor type 3 (MC3-R) have been evaluated in a murine model of experimental gout. Systemic treatment of mice with γ2-melanocyte-stimulating hormone (γ2-MSH) and the synthetic agonist MTII inhibited accumulation of KC, interleukin-1 beta (IL-1β), and PMN elicited by urate crystals in the peritoneal cavity. In vitro, macrophage (Mø) activation, determined as release of KC and IL-1β, was inhibited by γ2-MSH and MTII. The mixed MC3/4-R antagonist SHU9119 prevented the inhibitory actions of γ2-MSH and MTII in vitro and in vivo, whereas the selective MC4-R antagonist HS024 was without effect. Western blotting also showed the presence of MC3-R protein on murine peritoneal Mø. Furthermore, agonism at the MC3-R evoked accumulation of cAMP within the Mø, which was inhibited by SHU9119. Thus, naturally occurring melanocortins, as well as the synthetic long-acting compound MTII, activate MC3-R on peritoneal Mø to inhibit the experimental inflammatory response.

Item Type:Article
Research Community:University of Westminster > Life Sciences, School of
ID Code:10850
Deposited On:18 Jul 2012 16:38
Last Modified:18 Jul 2012 16:38

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