Modulatory activity of extracellular H+ and Zn2+ on ATP-responses at rP2X1 and rP2X3 receptors
Modulatory activity of extracellular H+ and Zn2+ on ATP-responses at rP2X1 and rP2X3 receptors
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DOI：
10.1038/sj.bjp.0702802
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发表时间：
1999-09-01
影响因子：
7.3
通讯作者：
Burnstock, G
中科院分区：
文献类型：
--
作者：
Wildman, SS;King, BF;Burnstock, G
1 .研究了细胞外H+和Zn2+对爪蟾卵母细胞表达的大鼠P2X(1) （rP2X(1)）和大鼠P2X(3) （rP2X(3)）受体atp反应的调节活性，并在电压箝位条件下进行了研究过氧化ATP （0.03-30 μ M, pH 7.5）在rP2X(1)受体（EC50值，300+/-7 nM）处引起内向电流。在pH 6.5和pH 5.5下，ATP效价分别降低了2 / 4和6 / 4，但没有改变ATP的最大效应。碱性条件（pH 8.0）没有改变。ATP activity.3过量ATP （0.01-300 μ M, pH 7.5）在rP2X(3)受体上引起向内电流（EC50值）。1.8+/-0.3 μ M)。ATP活性仅在pH 5.5时受到影响，在不改变最大ATP效应的情况下，激动剂的效力降低了15倍细胞外Zn2+以时间依赖性的方式抑制rP2X(1)受体的atp反应，预孵育20分钟为最佳（IC50值，1.0+/-0.2 μ M）。然而，Zn2+的作用与ph无关，表明Zn2+-和H+-对atp反应的抑制是通过独立的过程发生的细胞外Zn2+弱增强rP2X(3)受体的atp反应（EC50，值，11+/-1 μ M）。Zn2+的作用依赖于预孵育时间，在预孵育20 min后，Zn2+以浓度依赖的方式增强和抑制atp反应，但不依赖于ph综上所述，胞外H+和Zn2+均降低了rP2X(1)受体的ATP活性，且其作用是加性的。rP2X(3)受体的ATP活性对H+抑制不太敏感，相反，Zn2+以不依赖ph的方式增强了ATP活性。这些差异效应可能有助于在整个组织中区分P2X(1)和P2X(3)受体。
1 The modulatory activity of extracellular H+ and Zn2+ was examined on ATP-responses at rat P2X(1) (rP2X(1)) and rat P2X(3) (rP2X(3)) receptors expressed in Xenopus oocytes and studied under voltage-clamp conditions.2 Superfused ATP (0.03-30 mu M, at pH 7.5) evoked inward currents at rP2X(1) receptors (EC50 value, 300+/-7 nM). ATP potency was reduced 2 fold at pH 6.5, and 6 fold at pH 5.5, without altering the maximum ATP effect. Alkaline conditions (pH 8.0) did not alter. ATP activity.3 Superfused ATP (0.01-300 mu M, at pH 7.5) evoked inward currents at rP2X(3) receptors (EC50 value. 1.8+/-0.3 mu M). ATP activity was affected only at pH 5.5, reducing agonist potency 15 fold without altering the maximum ATP effect.4 Extracellular Zn2+ inhibited ATP-responses at rP2X(1) receptors in a time-dependent manner, a 20 min pre-incubation being optimal (IC50 value, 1.0+/-0.2 mu M). However, the Zn2+ effect was pH-independent, suggesting Zn2+- and H+-inhibition of ATP-responses occur through independent processes.5 Extracellular Zn2+ weakly potentiated ATP-responses at rP2X(3) receptors (EC50, value, 11+/-1 mu M). The Zn2+ effect was dependent on pre-incubation time and, with 20 min pre-incubation periods, Zn2+ potentiated then inhibited ATP-responses in a concentration-dependent, but pH-independent, manner.6 In summary, ATP activity at rP2X(1) receptors was decreased by both extracellular H+ and Zn2+ and their effects were additive. ATP activity at rP2X(3) receptors was less sensitive to H+-inhibition and, in contrast, was potentiated by Zn2+ in a pH-independent manner. These differential effects may help distinguish P2X(1), and P2X(3), receptors in whole tissues.