Mollereau C, Gouardères C, Dumont Y, Kotani M, Detheux M, Doods H, Parmentier M, Quirion R, Zajac J M
Institut de Pharmacologie et Biologie Structurale, 205 route de Narbonne, 31077 Toulouse, France.
Br J Pharmacol. 2001 May;133(1):1-4. doi: 10.1038/sj.bjp.0704049.
Neuropeptide FF (NPFF) is a part of a neurotransmitter system acting as a modulator of endogenous opioid functions. At this time, no non-peptide or peptide NPFF-antagonists have been discovered. Here, we demonstrate that Neuropeptide Y (NPY) ligands, in fact possess significant ability to interact with the human NPFF(2) receptors. NPY Y(1) antagonist BIBP3226 and mixed Y(1) antagonist/Y(4) agonist GR231118 are able to displace with low affinity, 50 -- 100 nM, the specific binding on NPFF receptors expressed in CHO cells as well as in rat dorsal spinal cord, an affinity however superior to those determined against Y(2), Y(4) or Y(5) receptors. Furthermore, BIBP3226 which is unable to inhibit the forskolin-stimulated cyclic AMP production mediated by NPFF(2) receptors, antagonizes the effect of NPFF, revealing the first antagonist of NPFF receptors. These properties of NPY ligands on Neuropeptide FF receptors must be considered when evaluating pharmacological activities of these drugs.
神经肽FF（NPFF）是作为内源性阿片样物质功能调节剂的神经递质系统的一部分。目前，尚未发现非肽或肽类NPFF拮抗剂。在此，我们证明神经肽Y（NPY）配体实际上具有与人类NPFF(2)受体相互作用的显著能力。NPY Y(1)拮抗剂BIBP3226和混合Y(1)拮抗剂/Y(4)激动剂GR231118能够以低亲和力（50 - 100 nM）取代在CHO细胞以及大鼠背脊髓中表达的NPFF受体上的特异性结合，然而这种亲和力优于针对Y(2)、Y(4)或Y(5)受体所测定的亲和力。此外，无法抑制由NPFF(2)受体介导的福斯高林刺激的环磷酸腺苷产生的BIBP3226可拮抗NPFF的作用，从而揭示了首个NPFF受体拮抗剂。在评估这些药物的药理活性时，必须考虑NPY配体在神经肽FF受体上的这些特性。
