Melanocortin-1 receptor-mediated signalling pathways activated by NDP-MSH and HBD3 ligands.

ABSTRACT: Binding of melanocortin peptide agonists to the melanocortin-1 receptor of melanocytes results in eumelanin production, whereas binding of the agouti signalling protein inverse agonist results in pheomelanin synthesis. Recently, a novel melanocortin-1 receptor ligand was reported. A ?-defensin gene mutation was found to be responsible for black coat colour in domestic dogs. Notably, the human equivalent, ?-defensin 3, was found to bind with high affinity to the melanocortin-1 receptor; however, the action of ?-defensin as an agonist or antagonist was unknown. Here, we use in vitro assays to show that ?-defensin 3 is able to act as a weak partial agonist for cAMP signalling in human embryonic kidney (HEK) cells expressing human melanocortin-1 receptor. ?-defensin 3 is also able to activate MAPK signalling in HEK cells stably expressing either wild type or variant melanocortin-1 receptors. We suggest that ?-defensin 3 may be a novel melanocortin-1 receptor agonist involved in regulating melanocyte responses in humans.

SUBMITTER: Beaumont KA 

PROVIDER: S-EPMC3994986 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature