Apparent species differences in the kinetic properties of P2X7 receptors
Apparent species differences in the kinetic properties of P2X7 receptors
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DOI：
10.1038/sj.bjp.0703302
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发表时间：
2000-05-01
影响因子：
7.3
通讯作者：
Michel, AD
中科院分区：
文献类型：
--
作者：
Hibell, AD;Kidd, EJ;Michel, AD
图1重组P2 X（7）受体对重复应用2 '-和3'-O-的反应的明显物种差异已经研究了（4-苯甲酰基苯甲酰基）-ATP（BzATP）。2重复应用100 μ M BzATP导致电流幅度逐渐增加（目前的增长）在小鼠和人类，而大鼠的P2 X（7）受体则没有。3电流的增长被认为反映了P2 X（7）离子通道向可渗透大分子的孔的进行性扩张（MW < 900），表明在大鼠P2 X（7）受体上没有发生通道扩张。然而，100 μ M BzATP在表达大鼠或人P2 X（7）受体的细胞中产生YO-PRO-1（MW 375）的快速流入。4然而，激动剂效力存在种属差异，因此100 μ M BzATP对大鼠P2 X（7）受体是超最大浓度，而对人或小鼠P2 X（7）受体不是。重要的是，当检查BzATP或ATP的次最大浓度时，在大鼠P2 X（7）受体处发生电流增长。5电流增长和YO-PRO-1蓄积的速率随激动剂浓度增加而增加，在大鼠和人中似乎更快，BzATP和ATP的效力为1.5- 2.5倍。在幼稚细胞中比在反复暴露于ATP的细胞中低10倍。7该研究表明，电流增长发生在小鼠、大鼠和人P2 X（7）受体上，但仅当使用次最大浓度的激动剂时。以前，电流增长被认为反映了P2 X（7）受体离子通道孔径的逐渐增加，然而，本研究的结果表明激动剂效力的逐渐增加也可能起作用。
1 Apparent species differences in the responses of recombinant P2X(7) receptors to repeated application of 2'- and 3'-O-(4-benzoylbenzoyl)-ATP (BzATP) have been investigated.2 Repeated application of 100 mu M BzATP resulted in a progressive increase in current magnitude (current growth) at mouse and human, but not rat P2X(7) receptors.3 Current growth was thought to reflect progressive dilation of the P2X(7) ion-channel to a pore permeable to large molecules (MW < 900), suggesting that channel dilation was not occurring at the rat P2X(7) receptor. However, 100 mu M BzATP produced a rapid influx of YO-PRO-1 (MW375) in cells expressing rat or human P2X(7) receptors.4 There were, however, species differences in agonist potency such that 100 mu M BzATP was a supra-maximal concentration at rat, but not human or mouse, P2X(7) receptors. Importantly, when sub-maximal concentrations of BzATP or ATP were examined, current growth occurred at rat P2X(7) receptors.5 The rate of current growth and YO-PRO-1 accumulation increased with agonist concentration and appeared more rapid at rat and human, than at mouse P2X(7) receptors.6 The potency of BzATP and ATP was 1.5-10 fold lower in naive cells than in cells repeatedly exposed to ATP.7 This study demonstrates that current growth occurs at mouse, rat and human P2X(7) receptors but only when using sub-maximal concentrations of agonist. Previously, current growth was thought to reflect the progressive increase in pore diameter of the P2X(7) receptor ion channel, however, the results of this study suggest a progressive increase in agonist potency may also contribute.