γ₂-Melanocyte stimulation hormone (γ₂-MSH) truncation studies results in the cautionary note that γ₂-MSH is not selective for the mouse MC3R over the mouse MC5R.
γ₂-Melanocyte stimulation hormone (γ₂-MSH) truncation studies results in the cautionary note that γ₂-MSH is not selective for the mouse MC3R over the mouse MC5R.
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DOI：
10.1016/j.peptides.2010.08.025
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发表时间：
2010-12
期刊：
影响因子：
3
通讯作者：
Haskell-Luevano C
中科院分区：
文献类型：
--
作者：
Joseph CG;Yao H;Scott JW;Sorensen NB;Marnane RN;Mountjoy KG;Haskell-Luevano C
黑素皮质素系统与多种生理途径有关，包括肥胖、饱腹感、能量平衡、性行为、色素沉着、钠调节、高血压等。基于对克隆的人黑素皮质素受体蛋白内源性黑素皮质素受体激动剂的研究，得出结论：γ-MSH相关激动剂配体对MC3与MC4和MC5受体具有选择性。为了了解和鉴定MC3R选择性重要的γ2-MSH的特定氨基酸，我们进行了N端和C端截断研究，并对小鼠Mc1和Mc3-5黑素皮质素受体上的28个配体进行了药理学特征研究。C-末端的Trp-Asp9-Arg10-Phe11残基对mMC3R的NM效力重要，Arg7-Trp8残基对mMC5R的NM效力重要。我们观察到了意想不到的结果，即几个C末端截短的类似物在mMC3和mMC5R上具有NM激动剂效力，这导致我们对小鼠和人的MC5R进行了并排比较研究。这些数据导致了在hMC5R的μMγ2-MSH类似物效价，这与以前的报道一致，但在mMC5R，观察到了NMγ2-MSH类似物效价。因此，这些数据支持这一假说，即啮齿类动物和人类的γ-msh相关配基的效力存在重要的物种特异性差异，这对于解释啮齿动物体内的生理研究至关重要。这些结果促使我们研究外周应用黑素皮质素激动剂对下丘脑MC3R、MC4R和MC5R基因表达水平的影响。超强非选择性NDP-MSH激动剂ip。与生理盐水对照组比较，下丘脑mMC3R和mMC5R基因表达水平显著降低。这些数据首次提供了外周给药NDP-MSH可以改变下丘脑黑素皮质素受体表达水平的数据。
The melanocortin system has been implicated in a multitude of physiological pathways including obesity, satiety, energy homeostasis, sexual behavior, pigmentation, sodium regulation, hypertension, and many others. Based upon studies of the endogenous melanocortin receptor agonists at the cloned human melanocortin receptor proteins, it was concluded that the γ-MSH related agonist ligands are selective for the MC3 versus the MC4 and MC5 receptors. In attempts to understand and identify the specific amino acids of γ2-MSH important for MC3R selectivity, we have performed N- and C-terminal truncation studies and pharmacologically characterized twenty-eight ligands at the mouse MC1 and MC3-5 melanocortin receptors. The C-terminal Trp-Asp9-Arg10-Phe11 residues are important for nM potency at the mMC3R and the Arg7-Trp8 residues are important for mMC5R nM potency. We observed the unanticipated results that several of the C-terminal truncated analogues possessed nM agonist potency at the mMC3 and mMC5Rs which lead us to performed a comparative side-by-side study of the mouse and human MC5R. These data resulted in μM γ2-MSH analogue potency at the hMC5R, consistent with previous reports, however at the mMC5R, nM γ2-MSH analogue potency was observed. Thus, these data support the hypothesis of important species specific differences in γ-MSH related ligand potency at the rodent versus human MC5R subtype that is critical for the interpretation of in vivo rodent physiological studies. These results prompted us to examine the affects of a peripherally administered melanocortin agonist on hypothalamic gene expression levels of the MC3R, MC4R, and MC5R. The super potent non-selective NDP-MSH agonist was administered i.p. and resulted in significantly decreased levels of mMC3R and mMC5R hypothalamic mRNA versus saline control. These data provide for the first time data demonstrating peripherally administered NDP-MSH can modify hypothalamic melanocortin receptor expression levels.
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影响因子：
2.9
作者：
CHEN, WB;SHIELDS, TS;CONE, RD
通讯作者：
CONE, RD
DOI：
10.1006/bbrc.1993.2125
发表时间：
1993-09-15
影响因子：
3.1
作者：
CHHAJLANI, V;MUCENIECE, R;WIKBERG, JES
通讯作者：
WIKBERG, JES
影响因子：
7.3
作者：
Cai, MY;Mayorov, AV;Hruby, VJ
通讯作者：
Hruby, VJ
DOI：
10.1034/j.1399-3011.2002.01966.x
发表时间：
2002-05-01
期刊：
JOURNAL OF PEPTIDE RESEARCH
影响因子：
--
作者：
Grieco, P;Balse-Srinivasan, P;Hruby, VJ
通讯作者：
Hruby, VJ
影响因子：
7.3
作者：
Grieco, P;Balse, PM;Hruby, VJ
通讯作者：
Hruby, VJ