Diinosine pentaphosphate:: an antagonist which discriminates between recombinant P2X3 and P2X2/3 receptors and between two P2X receptors in rat sensory neurones
Diinosine pentaphosphate:: an antagonist which discriminates between recombinant P2X3 and P2X2/3 receptors and between two P2X receptors in rat sensory neurones
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DOI：
10.1038/sj.bjp.0703404
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发表时间：
2000-07-01
影响因子：
7.3
通讯作者：
Burnstock, G
中科院分区：
文献类型：
--
作者：
Dunn, PM;Liu, M;Burnstock, G
1比较了三硝基苯基三磷酸腺苷(TNP-ATP)和五磷酸二肌苷(Ip(5)I)对非洲爪哇卵母细胞表达的重组P2X受体的拮抗作用，以及它们对脊神经节和结状神经节感觉神经元天然P2X受体的作用。2亚微摩尔浓度的TNP-ATP可抑制表达P2X(2/3)受体的卵母细胞对α，β-亚甲基，ATP(α，β-meATP)的缓慢脱敏反应。3结状神经节神经元对α，β-meATP的反应是缓慢脱敏的内向电流。在以快速脱敏内向电流反应的DRG神经元中，TNP-ATP(IC50，20 nM)可抑制这种反应，IC50为0.8 nM。这些反应也被Ip(5)I抑制，IC_(50)为0.1微米。这两种拮抗剂都能抑制同质的P2X(3)受体。5一些DRG神经元对α，β-meATP的反应是由瞬时和持续成分组成的双相内向电流。Ip(5)I可使瞬时电流消失，但持续成分不受影响。6总之，Ip(5)I是同质的P2X3受体的有效拮抗剂，而不是异构体的P2Y(2/3)受体的拮抗剂，因此Ip(5)I可以作为一种有用的工具来阐明天然的P2X受体的亚单位组成。
1 We have compared the antagonist activity of trinitrophenyl-ATP (TNP-ATP) and diinosine pentaphosphate (Ip(5)I) on recombinant P2X receptors expressed in Xenopus oocytes with their actions at native P2X receptors in sensory neurones from dorsal root and nodose ganglia.2 Slowly-desensitizing responses to alpha,beta-methyfene, ATP (alpha,beta-meATP) recorded from oocytes expressing P2X(2/3) receptors were inhibited by TNP-ATP at sub-micromolar concentrations. However, Ip(5)I at concentrations up to 30 mu M was without effect.3 Nodose ganglion neurones responded to alpha,beta-meATP with slowly-desensitizing inward currents. These were inhibited by TNP-ATP (IC50, 20 nM), but not by Ip(5)I at concentrations up to 30 mu M.4 In DRG neurones that responded to ATP with a rapidly-desensitizing inward current, the response was inhibited by TNP-ATP with an IC50 of 0.8 nM. These responses were also inhibited by Ip(5)I with an IC50 of 0.1 mu M. Both antagonists an known to inhibit homomeric P2X(3) receptors.5 Some DRG neurones responded to alpha,beta-meATP with a biphasic inward current, consisting of transient and sustained components. While the transient current was abolished by 1 mu M Ip(5)I, the sustained component remained unaffected.6 In conclusion, Ip(5)I is a potent antagonist at homomeric P2X3 receptors but not at heteromeric P2Y(2/3) receptors, and therefore should be a useful tool for elucidating the subunit composition of native P2X receptors.