Soto F, Garcia-Guzman M, Gomez-Hernandez J M, Hollmann M, Karschin C, Stühmer W
Department of Molecular Biology of Neuronal Signals, Max Planck Institute for Experimental Medicine, Gottingen, Germany.
Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3684-8. doi: 10.1073/pnas.93.8.3684.
Extracellular ATP exerts pronounced biological actions in virtually every organ or tissue that has been studied. In the central and peripheral nervous system, ATP acts as a fast excitatory transmitter in certain synaptic pathways [Evans, R.J., Derkach, V. & Surprenant, A. (1992) Nature (London) 357, 503-505; Edwards, F.A., Gigg, A.J. & Colquhoun, D. (1992) Nature (London) 359, 144-147]. Here, we report the cloning and characterization of complementary DNA from rat brain, encoding an additional member (P2X4) of the emerging multigenic family of ligand-gated ATP channels, the P2X receptors. Expression in Xenopus oocytes gives an ATP-activated cation-selective channel that is highly permeable to Ca2+ and whose sensitivity is modulated by extracellular Zn2+. Surprisingly, the current elicited by ATP is almost insensitive to the common P2X antagonist suramin. In situ hybridization reveals the expression of P2X4 mRNA in central nervous system neurons. Northern blot and reverse transcription-PCR (RT-PCR) analysis demonstrate a wide distribution of P2X4 transcripts in various tissues, including blood vessels and leukocytes. This suggests that the P2X4 receptor might mediate not only ATP-dependent synaptic transmission in the central nervous system but also a wide repertoire of biological responses in diverse tissues.
细胞外ATP在几乎每一个已被研究的器官或组织中都发挥着显著的生物学作用。在中枢和外周神经系统中，ATP在某些突触通路中作为一种快速兴奋性递质发挥作用[埃文斯，R.J.，德尔卡奇，V. & 苏普雷南特，A.（1992年）《自然》（伦敦）357, 503 - 505；爱德华兹，F.A.，吉格，A.J. & 科尔昆，D.（1992年）《自然》（伦敦）359, 144 - 147]。在此，我们报告了从大鼠脑中克隆并鉴定互补DNA，其编码配体门控ATP通道新兴多基因家族（P2X受体）的另一个成员（P2X4）。在非洲爪蟾卵母细胞中的表达产生了一种ATP激活的阳离子选择性通道，该通道对Ca2+具有高度通透性，其敏感性受细胞外Zn2+调节。令人惊讶的是，ATP引发的电流对常见的P2X拮抗剂苏拉明几乎不敏感。原位杂交显示P2X4 mRNA在中枢神经系统神经元中表达。Northern印迹和逆转录 - PCR（RT - PCR）分析表明P2X4转录本在包括血管和白细胞在内的各种组织中广泛分布。这表明P2X4受体可能不仅介导中枢神经系统中依赖ATP的突触传递，还介导多种组织中的广泛生物学反应。
