The William Harvey Research Institute, Charterhouse Square, London, England
Correspondence: Stephen J. Getting, Ph.D., Department of Biochemical Pharmacology, The William Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, England. E-mail: S.J.Getting{at}mds.qmw.ac.uk
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
2-melanocyte-stimulating hormone (
2-MSH)
and the synthetic agonist MTII inhibited accumulation of KC,
interleukin-1 beta (IL-1ß), and PMN elicited by urate crystals in the
peritoneal cavity. In vitro, macrophage (Mø) activation,
determined as release of KC and IL-1ß, was inhibited by
2-MSH and MTII. The mixed MC3/4-R antagonist SHU9119
prevented the inhibitory actions of
2-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.
Key Words:
2-MSH MTII KC IL-1ß inflammation
This article has been cited by other articles:
![]() |
G. S. Cooke, S. J. Campbell, S. Bennett, C. Lienhardt, K. P. W. J. McAdam, G. Sirugo, O. Sow, P. Gustafson, F. Mwangulu, P. van Helden, et al. Mapping of a Novel Susceptibility Locus Suggests a Role for MC3R and CTSZ in Human Tuberculosis Am. J. Respir. Crit. Care Med., July 15, 2008; 178(2): 203 - 207. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Catania The melanocortin system in leukocyte biology J. Leukoc. Biol., February 1, 2007; 81(2): 383 - 392. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Getting, C. W. Lam, G. Leoni, F. N. E. Gavins, P. Grieco, and M. Perretti [D-Trp8]-{gamma}-Melanocyte-Stimulating Hormone Exhibits Anti-Inflammatory Efficacy in Mice Bearing a Nonfunctional MC1R (Recessive Yellow e/e Mouse) Mol. Pharmacol., December 1, 2006; 70(6): 1850 - 1855. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Getting, C. W. Lam, A. S. Chen, P. Grieco, and M. Perretti Melanocortin 3 receptors control crystal-induced inflammation FASEB J, November 1, 2006; 20(13): 2234 - 2241. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Kang, K. W. McIntyre, K. M. Gillooly, Y. Yang, J. Haycock, S. Roberts, A. Khanna, T. F. Herpin, G. Yu, X. Wu, et al. A selective small molecule agonist of the melanocortin-1 receptor inhibits lipopolysaccharide-induced cytokine accumulation and leukocyte infiltration in mice J. Leukoc. Biol., October 1, 2006; 80(4): 897 - 904. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. R. Vulliemoz, E. Xiao, L. Xia-Zhang, M. Ferin, and S. L. Wardlaw Melanocortin Modulation of Inflammatory Cytokine and Neuroendocrine Responses to Endotoxin in the Monkey Endocrinology, April 1, 2006; 147(4): 1878 - 1883. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Dalbeth and D. O. Haskard Mechanisms of inflammation in gout Rheumatology, September 1, 2005; 44(9): 1090 - 1096. [Full Text] [PDF] |
||||
![]() |
C. W. Lam, S. J. Getting, and M. Perretti In Vitro and In Vivo Induction of Heme Oxygenase 1 in Mouse Macrophages following Melanocortin Receptor Activation J. Immunol., February 15, 2005; 174(4): 2297 - 2304. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Getting, C. Di Filippo, C. W. Lam, F. Rossi, and M. D'Amico Investigation into the Potential Anti-Inflammatory Effects of Endothelin Antagonists in a Murine Model of Experimental Monosodium Urate Peritonitis J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 90 - 97. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Catania, S. Gatti, G. Colombo, and J. M. Lipton Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation Pharmacol. Rev., March 1, 2004; 56(1): 1 - 29. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Getting, H. B. Schioth, and M. Perretti Dissection of the Anti-Inflammatory Effect of the Core and C-Terminal (KPV) {alpha}-Melanocyte-Stimulating Hormone Peptides J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 631 - 637. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Getting, H. C. Christian, C. W. Lam, F. N. E. Gavins, R. J. Flower, H. B. Schioth, and M. Perretti Redundancy of a Functional Melanocortin 1 Receptor in the Anti-inflammatory Actions of Melanocortin Peptides: Studies in the Recessive Yellow (e/e) Mouse Suggest an Important Role for Melanocortin 3 Receptor J. Immunol., March 15, 2003; 170(6): 3323 - 3330. [Abstract] [Full Text] [PDF] |
||||