CNRS/IPBS (Institut de Pharmacologie et Biologie Structurale), 205 route de Narbonne, 31077 Toulouse Cedex, France.
Peptides. 2010 Feb;31(2):215-20. doi: 10.1016/j.peptides.2009.11.020. Epub 2009 Nov 26.
This study presents the binding and functional properties of the mouse NPFF(2) (mNPFF(2)) receptor, in comparison with its human counterpart (hNPFF(2)). Binding experiments were performed by using the NPFF(2) selective radioligand [(3)H]-EYF in membranes from CHO cells transfected with mouse and human NPFF(2) receptors and compared to membranes from mouse olfactory bulb, the brain region expressing the highest density of NPFF(2) receptors in mouse. mNPFF(2) receptors exhibited a high affinity (Kd=0.2-0.4 nM) for [(3)H]-EYF, comparable to that of hNPFF(2) receptors. Also, the binding selectivity profile of mNPFF(2) receptors was comparable to that of hNPFF(2) receptors, except for three ligands (NPSF, NPVF, RF9) that were about tenfold more potent and active on mouse receptors than on human receptors. In particular, compared to hNPFF(2) receptors, mNPFF(2) receptors were less discriminative towards the proNPFF(B)-derived peptide. This suggests some species-related differences in the binding properties of NPFF(2) receptors that could have repercussion when evaluating the pharmacological properties of drugs in vivo.
本研究比较了鼠 NPFF(2)(mNPFF(2))受体与人 NPFF(2)(hNPFF(2))受体的结合和功能特性。通过使用 NPFF(2)选择性放射性配体[(3)H]-EYF 在转染了鼠和人 NPFF(2)受体的 CHO 细胞的膜中进行结合实验，并与来自鼠嗅球的膜进行比较，嗅球是鼠脑中表达 NPFF(2)受体密度最高的区域。mNPFF(2)受体对[(3)H]-EYF 表现出高亲和力(Kd=0.2-0.4 nM)，与 hNPFF(2)受体相当。此外，mNPFF(2)受体的结合选择性谱与 hNPFF(2)受体相当，除了三种配体(NPSF、NPVF、RF9)，它们对鼠受体的效力和活性比人受体高约十倍。特别是与 hNPFF(2)受体相比，mNPFF(2)受体对 proNPFF(B)衍生肽的辨别力较低。这表明 NPFF(2)受体的结合特性存在一些种属相关的差异，这可能会对体内评估药物的药理学特性产生影响。
