Jørgensen J C, Fuhlendorff J, Schwartz T W
Department of Clinical Chemistry, University of Copenhagen, Denmark.
Eur J Pharmacol. 1990 Sep 4;186(1):105-14. doi: 10.1016/0014-2999(90)94065-6.
The biological effects of neuropeptide Y (NPY), rat pancreatic polypeptide (rPP), hybrid analogs of NPY and PP, and C-terminal fragments of NPY were studied in the field-stimulated rat vas deferens model. The results were correlated with peptide binding experiments in Y1 and PP receptor assays on rat PC-12 cells and Y2 receptors on porcine hippocampal membranes. NPY and rPP inhibited the electrically induced contractions in the vas deferens with an IC50 of 25 and 22 nM respectively. However, in contrast to NPY, rPP could not totally block muscle activity. The inhibitory action of the long C-terminal fragment of NPY, NPY-(19-36) and NPY-(11-36), indicated that NPY acts through a Y2 receptor in the vas deferens. The structural basis for the differential recognition of NPY and PP by Y2 receptors and partly also by PP receptors, could be defined with hybrid analogs of PP and NPY. The analogs, [Ile31,Gln34]PP and [Leu31,Pro33]NPY reacted in the vas deferens preparation in accordance with their relative potency in the Y2 and PP receptor assays. [Ile31,Gln34]PP, which bound to the Y2 receptor like NPY, was also able to block the part of the contractile response which was resistant to rPP. It is concluded that in the vas deferens, PP-fold peptides act through two types of receptors: Y2 and PP, and that residues in the C-terminal part of the molecules determine the differential recognition of the peptides by these receptor types.
在电场刺激大鼠输精管模型中研究了神经肽Y（NPY）、大鼠胰多肽（rPP）、NPY与PP的杂交类似物以及NPY的C末端片段的生物学效应。将结果与大鼠PC - 12细胞上Y1和PP受体测定以及猪海马膜上Y2受体的肽结合实验相关联。NPY和rPP分别以25 nM和22 nM的IC50抑制输精管中的电诱导收缩。然而，与NPY不同，rPP不能完全阻断肌肉活动。NPY的长C末端片段NPY-(19 - 36)和NPY-(11 - 36)的抑制作用表明NPY通过输精管中的Y2受体发挥作用。Y2受体以及部分PP受体对NPY和PP的差异识别的结构基础，可以通过PP和NPY的杂交类似物来确定。类似物[Ile31,Gln34]PP和[Leu31,Pro33]NPY在输精管制剂中的反应与其在Y2和PP受体测定中的相对效力一致。[Ile31,Gln34]PP像NPY一样与Y2受体结合，也能够阻断对rPP有抗性的部分收缩反应。得出的结论是，在输精管中，PP折叠肽通过两种类型的受体发挥作用：Y2和PP，并且分子C末端部分的残基决定了这些受体类型对肽的差异识别。
