Pharmacological characterization of the mouse NPFF2 receptor

This study presents the binding and functional properties of the mouse NPFF2 (mNPFF2) receptor, in comparison with its human counterpart (hNPFF2). Binding experiments were performed by using the NPFF2 selective radioligand [3H]-EYF in membranes from CHO cells transfected with mouse and human NPFF2 receptors and compared to membranes from mouse olfactory bulb, the brain region expressing the highest density of NPFF2 receptors in mouse. mNPFF2 receptors exhibited a high affinity (Kd = 0.2–0.4 nM) for [3H]-EYF, comparable to that of hNPFF2 receptors. Also, the binding selectivity profile of mNPFF2 receptors was comparable to that of hNPFF2 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 hNPFF2 receptors, mNPFF2 receptors were less discriminative towards the proNPFFB-derived peptide. This suggests some species-related differences in the binding properties of NPFF2 receptors that could have repercussion when evaluating the pharmacological properties of drugs in vivo.