Irreversible binding kinetics of neuropeptide y Ligands to Y2 but not to Y1 and Y5 receptors
Irreversible binding kinetics of neuropeptide y Ligands to Y2 but not to Y1 and Y5 receptors
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DOI：
10.1159/000085897
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发表时间：
2005-01-01
期刊：
影响因子：
3.1
通讯作者：
Neysari, S
中科院分区：
文献类型：
--
作者：
Dautzenberg, FM;Neysari, S
测试了神经肽Y （NPY）受体1型（Y-1）、2型（Y- 2）和5型（Y-5）结合放射性标记的NPY或PYY的动力学特性。重组（HEK293细胞）和内源性（SK-N-MC细胞）人Y-1和重组小鼠Y-5受体快速结合和解离。重组（HEK293）和内源性（SMS-KAN）人Y-2受体与Y-1受体的结合程度与Y-1受体相当，但在长时间孵育（bbb8 h）后，两种放射性标记的解离程度仅为极小（约20%）。此外，一旦结合开始，肽和小分子Y-2配体都不能有效地竞争与Y-2受体的结合。y -2选择性拮抗剂BIIE0246在加入激动剂前预孵育30分钟，在功能测试中表现为不可克服的拮抗剂，但与激动剂共同应用时是竞争性拮抗剂。这些数据表明，与Y-1和Y-5受体相比，Y-2受体以不可逆的方式结合其配体。版权所有(C) 2005 S. Karger AG，巴塞尔。
Neuropeptide Y (NPY) receptors type 1 (Y-1), type 2 Y-2) and type 5 (Y-5) were tested for their kinetic properties to bind radiolabeled NPY or PYY. Rapid association and dissociation was observed with recombinant (HEK293 cells) and endogenous (SK-N-MC cells) human Y-1 and recombinant mouse Y-5 receptors. Recombinant ( HEK293) and endogenous (SMS-KAN) human Y-2 receptors bound both radiolabels comparable to the Y-1 receptors, but only minimal (similar to 20%) dissociation of both radiolabels was observed after long incubation time (>8 h). Furthermore, neither peptide nor small molecule Y-2 ligands efficiently competed for binding to Y 2 receptors once association binding had been initiated. The Y-2-selective antagonist BIIE0246 behaved as an insurmountable antagonist in functional assays when pre-incubated for 30 min before agonist addition, but was a competitive antagonist when co-applied with the agonist. These data show that Y-2 receptors in contrast to Y-1 and Y-5 receptors bind their ligands in an irreversible manner. Copyright (C) 2005 S. Karger AG, Basel.