Properties of the novel ATP-gated ionotropic receptor composed of the P2X(1) and P2X(5) isoforms.
Properties of the novel ATP-gated ionotropic receptor composed of the P2X(1) and P2X(5) isoforms.
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DOI：
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发表时间：
1999-10
影响因子：
3.6
通讯作者：
W. Haines;G. Torres;M. Voigt;Terrance M. Egan
中科院分区：
文献类型：
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作者：
W. Haines;G. Torres;M. Voigt;Terrance M. Egan
我们最近报道，当在人胚胎肾 293 细胞中共表达时，P2X(1) 和 P2X(5) 亚型形成了一种新型异源寡聚 P2X 受体 ()。本文更完整地描述了这种新型受体的药理学。将 ATP 短暂施加到瞬时表达 P2X(1/5) 受体的电压钳制细胞上，会产生双相电流，该电流迅速达到峰值，然后衰减至持续稳定水平。 ATP 的冲刷伴随着内向电流的明显尾部的产生和消失。 EC(50) 值是根据一系列激动剂的浓度-反应曲线确定的。激动剂效力的顺序为ATP>/=2甲硫基ATP>腺苷5'-O-(3-硫代三磷酸)>α,β-亚甲基ATP>ADP>CTP。 α,β-亚甲基 ADP、UTP、GTP 和 AMP 无效。只有 ATP 和 2 甲硫基 ATP 是完全激动剂。 IC(50) 值是根据三种常用嘌呤能拮抗剂的浓度-反应曲线确定的。苏拉明和磷酸吡哆醛-6-偶氮苯基-2', 4'-二磺酸对 P2X(1) 和 P2X(1/5) 受体等价。然而，P2X(1/5) 受体对TNP-ATP 的敏感性远低于P2X(1) 受体。峰值 ATP 门控电流的幅度对 [Ca(2+)](O) (1-30 mM) 的变化相对不敏感。最后，低浓度的磷酸吡哆醛-6-偶氮苯基-2', 4'-二磺酸和提高[Ca(2+)](O)可增强平台电流。这些结果提供了关于重组P2X(1/5)受体通道的药理学特征的额外信息，并为进一步评估天然组织中ATP诱导的电流提供了基础。
We recently reported that a novel hetero-oligomeric P2X receptor is formed from the P2X(1) and P2X(5) isoforms when coexpressed in human embryonic kidney 293 cells (). A more complete description of the pharmacology of this novel receptor is presented here. A brief application of ATP to a voltage-clamped cell transiently expressing P2X(1/5) receptors resulted in a biphasic current that rapidly reached a peak and then decayed to a sustained plateau. Washout of ATP was accompanied by generation and fade of a pronounced tail of inward current. EC(50) values were determined from concentration-response curves for a range of agonists. The rank order of agonist potency was ATP >/= 2 methylthio ATP > adenosine 5'-O-(3-thiotriphosphate) > alpha,beta-methylene ATP > ADP > CTP. alpha,beta-methylene ADP, UTP, GTP, and AMP were ineffective. Only ATP and 2 methylthio ATP were full agonists. IC(50) values were determined from concentration-response curves for three commonly used purinergic antagonists. Suramin and pyridoxal phosphate-6-azophenyl-2', 4'-disulfonic acid were equipotent at P2X(1) and P2X(1/5) receptors; however, the P2X(1/5) receptor was much less sensitive to TNP-ATP than was the P2X(1) receptor. The amplitude of peak ATP-gated current was relatively insensitive to changes in [Ca(2+)](O) (1-30 mM). Finally, plateau currents were potentiated by low concentrations of pyridoxal phosphate-6-azophenyl-2', 4'-disulfonic acid and by raising [Ca(2+)](O). These results provide additional information on the pharmacological profile of the recombinant P2X(1/5) receptor channel and provide a basis to further evaluate ATP-induced currents in native tissues.