King B F, Townsend-Nicholson A
Autonomic Neuroscience Institute, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, Hampstead, NW3 2PF, London, UK.
J Auton Nerv Syst. 2000 Jul 3;81(1-3):164-70. doi: 10.1016/s0165-1838(00)00134-x.
The beginning of the last decade heralded three important and sequential developments in our understanding of cell-to-cell signalling by extracellular ATP via its cell surface receptors, the P2 purinoceptors. One major development in ATP signalling culminated in a timely review in 1991, when it was established in the clearest of terms that ATP receptors exploited discrete signal transduction pathways (Dubyak, G.R., 1991. Signal transduction by P2-purinergic receptors for extracellular ATP. Am. J. Respir. Cell. Mol. Biol. 4, 295-300; and later in Dubyak, G.R., El-Moatassim, C., 1993. Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides. Am. J. Physiol. 265, C577-C606). Henceforth, it was universally acknowledged that some P2 purinoceptors interacted with heterotrimeric G-proteins to activate intracellular signalling cascades (metabotropic ATP receptors), whereas others contained intrinsic ion-channels (ionotropic ATP receptors). A second key development can be traced to 1992, from the discovery that ATP receptors were involved in excitatory neurotransmission in the CNS and PNS (Edwards, F.A., Gibb, A.J., Colquhoun, D., 1992. ATP receptor-mediated synaptic currents in the central nervous system. Nature 359, 144-147; Evans, R.J., Derkach, V., Surprenant, A., 1992. ATP mediates fast synaptic transmission in mammalian neurons. Nature 357, 503-505; Silinsky, E.M., Gerzanich, V., Vanner, S.M., 1992. ATP mediates excitatory synaptic transmission in mammalian neurones. Br. J. Pharmacol., 106, 762-763). Thereafter, it was accepted that ATP could play a neurotransmitter and/or modulatory role throughout the entire nervous system. The third key development stemmed from the isolation of a cDNA, from chick brain, encoding a metabotropic ATP receptor (Webb, T.E., Simon, J., Krishek, B.J., Bateson, A.N., Smart, T.G., King, B.F., Burnstock, G., Barnard, E.A., 1993. Cloning and functional expression of a brain G-protein-coupled ATP receptor. FEBS Lett. 324, 219-225). The cloning of a membrane protein serving as an ATP receptor ignited a widespread international interest in purinergic signalling. Investigators at University College London (UCL) - colleagues and associates of Geoffrey Burnstock - were at the forefront of this rapid phase of discovery. In this review, we highlight the UCL experience when the fields of molecular biology, physiology and cell biology converged to help advance our understanding of ATP as an extracellular signalling molecule.
过去十年伊始，在我们对细胞外ATP通过其细胞表面受体（P2嘌呤能受体）进行细胞间信号传导的理解方面，出现了三项重要且相继的进展。ATP信号传导的一项主要进展在1991年适时地进行了总结，当时已明确证实ATP受体利用离散的信号转导途径（杜比亚克，G.R.，1991年。细胞外ATP的P2 - 嘌呤能受体介导的信号转导。《美国呼吸细胞与分子生物学杂志》4，295 - 300；以及后来的杜比亚克，G.R.，埃尔 - 莫塔西姆，C.，1993年。细胞外ATP和其他核苷酸通过P2 - 嘌呤能受体的信号转导。《美国生理学杂志》265，C577 - C606）。此后，人们普遍认识到一些P2嘌呤能受体与异源三聚体G蛋白相互作用以激活细胞内信号级联反应（代谢型ATP受体），而其他一些则含有内在离子通道（离子型ATP受体）。第二项关键进展可追溯到1992年，源于发现ATP受体参与中枢神经系统和外周神经系统的兴奋性神经传递（爱德华兹，F.A.，吉布，A.J.，科尔昆，D.，1992年。中枢神经系统中ATP受体介导的突触电流。《自然》359，144 - 147；埃文斯，R.J.，德尔卡奇，V.，苏普伦南特，A.，1992年。ATP介导哺乳动物神经元中的快速突触传递。《自然》357，503 - 505；西林斯基，E.M.，格扎尼奇，V.，万纳，S.M.，1992年。ATP介导哺乳动物神经元中的兴奋性突触传递。《英国药理学期刊》106，762 - 763）。此后，人们接受了ATP在整个神经系统中可以发挥神经递质和/或调节作用。第三项关键进展源于从鸡脑中分离出一种编码代谢型ATP受体的cDNA（韦伯，T.E.，西蒙，J.，克里舍克，B.J.，贝茨森，A.N.，斯马特，T.G.，金，B.F.，伯恩斯托克，G.，巴纳德，E.A.，1993年。脑G蛋白偶联ATP受体的克隆与功能表达。《欧洲生物化学会联合会快报》324，219 - 225）。作为ATP受体的膜蛋白的克隆引发了国际上对嘌呤能信号传导的广泛关注。伦敦大学学院（UCL）的研究人员——杰弗里·伯恩斯托克的同事和伙伴——处于这一快速发现阶段的前沿。在本综述中，我们重点介绍了分子生物学、生理学和细胞生物学领域融合时伦敦大学学院的经历，这有助于推动我们对ATP作为细胞外信号分子的理解。
