| Abstrakt: |
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 vitroand 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. |
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