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

The effects of the natural and synthetic ligands for the melanocortin recep tor type 3 (MCS-R) have been evaluated in a murine model of experimental go ut, Systemic treatment of mice with gamma (2)-melanocyte-stimulating hormon e (gamma (2)-MSH) and the synthetic agonist MTII inhibited accumulation of KC, interleukin-1 beta (IL-1 beta), and PMN elicited by urate crystals in t he peritoneal cavity. In vitro, macrophage (MO) activation, determined as r elease of KC and IL-1 beta, was inhibited by gamma (2)-MSH and MTII, The mi xed MC3/4-R antagonist SHU9119 prevented the inhibitory actions of gamma (2 )-MSH and MTII in vitro and in vivo, whereas the selective MC4-R antagonist HSO24 was without effect. Western blotting also showed the presence of MC3 -R protein on murine peritoneal MO. Furthermore, agonism at the MC3-R evoke d accumulation of cAMP within the Mg, which was inhibited by SMU9119, Thus, naturally occurring melanocortins, as well as the synthetic long-acting co mpound MTII, activate MC3-R oil peritoneal Md to inhibit the experimental i nflammatory response.