Research Department of Neuroscience, Pharmacology & Physiology (NPP), University College London (UCL), Gower Street, London, WC1E 6BT, UK.
Purinergic Signal. 2021 Mar;17(1):25-31. doi: 10.1007/s11302-020-09747-6. Epub 2020 Oct 30.
The synaptic event called the inhibitory junction potential (IJP) was arguably one of the more important discoveries made by Burnstock and arguably one of his finer legacies. The discovery of the IJP fundamentally changed how electromechanical coupling was visualised in gastrointestinal smooth muscle. Its discovery also set in motion the search for novel inhibitory neurotransmitters in the enteric nervous system, eventually leading to proposal that ATP or a related nucleotide was a major inhibitory transmitter. The subsequent development of purinergic signalling gave impetus to expanding the classification of surface receptors for extracellular ATP, not only in the GI tract but beyond, and then led to successive phases of medicinal chemistry as the P2 receptor field developed. Ultimately, the discovery of the IJP led to the successful cloning of the first P2Y receptor (chick P2Y1) and expansion of mammalian ATP receptors into two classes: metabotropic P2Y receptors (encompassing P2Y1, P2Y2, P2Y4, P2Y6, P2Y11-14 receptors) and ionotropic P2X receptors (encompassing homomeric P2X1-P2X7 receptors). Here, the causal relationship between the IJP and P2Y1 is explored, setting out the milestones reached and achievements made by Burnstock and his colleagues.
被称为抑制性突触后电位（IJP）的突触事件，可以说是班克斯特（Burnstock）做出的更重要的发现之一，也是他更杰出的贡献之一。IJP 的发现从根本上改变了人们对胃肠平滑肌中机电耦联的看法。它的发现也引发了在肠神经系统中寻找新型抑制性神经递质的研究，最终提出 ATP 或相关核苷酸是主要的抑制性递质。随后嘌呤能信号的发展推动了对细胞外 ATP 表面受体分类的扩展，不仅在胃肠道，而且在胃肠道之外，然后随着 P2 受体领域的发展，相继进入了药物化学的各个阶段。最终，IJP 的发现导致了第一个 P2Y 受体（鸡 P2Y1）的成功克隆，并将哺乳动物 ATP 受体扩展为两类：代谢型 P2Y 受体（包括 P2Y1、P2Y2、P2Y4、P2Y6、P2Y11-14 受体）和离子型 P2X 受体（包括同源 P2X1-P2X7 受体）。本文探讨了 IJP 与 P2Y1 之间的因果关系，阐述了班克斯特及其同事取得的里程碑和成就。
