Regulation of TNF-α secretion by a specific melanocortin-1 receptor peptide agonist

被引：25
|
作者：
Ignar, DM
Andrews, JL
Jansen, M
Eilert, MM
Pink, HM
Lin, PY
Sherrill, RG
Szewczyk, JR
Conway, JG
机构：
[1] GlaxoSmithKline, Dept Metab Dis, Res Triangle Pk, NC 27709 USA
[2] GlaxoSmithKline, Dept Mol Pharmacol, Res Triangle Pk, NC 27709 USA
[3] GlaxoSmithKline, Dept Med Chem, Res Triangle Pk, NC 27709 USA
来源：
PEPTIDES | 2003年 / 24卷 / 05期
关键词：
melanocortin; TNF-alpha; alpha-MSH; melanocortin-1;
D O I：
10.1016/S0196-9781(03)00127-X
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The lack of specific pharmacological tools has impeded the evaluation of the role of each melanocortin receptor (MCR) subtype in the myriad physiological effects of melanocortins. 154N-5 is an octapeptide (MFRdWFKPV-NH2) that was first identified as an MC1R antagonist in Xenopus melanophores [J. Biol. Chem. 269 (1994) 29846]. In this manuscript, we show that 154N-5 is a specific agonist for human and murine MC1R. The peptide has negligible activity at MC3R and MC4R and is 25-fold less potent and a weak agonist at MC5R. 154N-5 was tested in both a cellular and an animal model of tumor necrosis factor-alpha (TNF-alpha) secretion. The inhibitory efficacy of 154N-5 on TNF-alpha secretion in both models was similar to the nonselective agonist NDP-alpha-melanocyte stimulating hormone (NDP-alphaMSH), thus, we conclude that inhibition of TNF-alpha secretion by melanocortin peptides is mediated by MC1R. 154N-5 is a valuable new tool for the evaluation of specific contribution of MC1R agonism to physiological and pathological processes. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码：709 / 716
页数：8
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