New highly specific agonistic peptides for human melanocortin MC1 receptor☆

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

“…Two MC1R-selective agonists, MS05 and MS09 (Szardenings et al, 2000), down-regulated expression and secretion of endothelial cell selectin (E-selectin), vascular cell adhesion molecule (VCAM), and intercellular adhesion molecule (ICAM), in human dermal vascular endothelial cells treated with tumor necrosis factor ␣ (TNF-␣) . Furthermore, both MS05 and the MS09 inhibited TNF-␣-induced activation of NF-B in endothelial cells.…”

Melanocortin 1 Receptor Agonists Reduce Proteinuria

“…11 ␣-melanocyte stimulating hormone (␣-MSH) is also a small endogenous peptide hormone, structurally related to ACTH, which binds all of the MCRs except MC2R. MS05 is a peptide of 13 amino acids specific for human MC1R, 12 which has been used in in vitro and in vivo studies but not in renal research. 13 The mechanism by which ACTH mediates its effect on proteinuria is still unknown and no one seems to have addressed the question.…”

Dissection of the Anti-Inflammatory Effect of the Core and C-Terminal (KPV) α-Melanocyte-Stimulating Hormone Peptides

“…To gain some information on the MC-R potentially involved in these actions, the effect of the selective MC1-R agonist MS05 (Szardenings et al, 2000) was evaluated, finding that it was inactive in this model. Interestingly, MS05 has been found to be inactive in models of white blood cell recruitment and consequent tissue injury (Guarini et al, 2002;Getting et al, 2003).…”

“…KPV failed to evoke a cAMP response in mouse peritoneal MØ, confirming that the core region (HFRW) is required for binding and activation of the receptor . Conversely, the MC1-R agonist MS05, which has very low affinity for the MC3-R (Szardenings et al, 2000), failed to cause cAMP accumulation. The failure of KPV to induce cAMP has previously been observed in RAW264.7 macrophages ) and in cells transfected with different melanocortin receptors as reported in a recent review .…”

“…The melanocortin peptides Ac-Nle 4 -c[Asp 5 ,D-Phe 7 ,Lys 10 ]NH 2 ACTH4-10 (MTII; 9.3 nmol) (Al-Obeidi et al, 1989), ␣-MSH (6 nmol), KPV (3-88 nmol), H-Ser-Ser-Ile-Ile-Ser-His-Phe-Arg-Trp-Gly-LysPro-Val-NH 2 (MS05; 0.66 -66 nmol) (Szardenings et al, 2000;Getting et al, 2003), ␣-MSH 6 -9 (HFRW; 104 nmol), or PBS (100 l) was administered s.c. either alone or in combination with the MC3/4-R antagonist Ac-Nle ]NH 2 ACTH4-10) (SHU9119; 9 nmol) (Hruby et al, 1995). MSU crystals were given i.p.…”