Purinergic signalling: from discovery to current developments.

Purinergic signalling: from discovery to current developments.
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DOI:
10.1113/expphysiol.2013.071951
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发表时间:
2014-01
影响因子:
2.7
通讯作者:
Burnstock G
Burnstock G
中科院分区:
医学4区
文献类型:
--
作者:
Burnstock G

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本次审查的主题是什么?这是一个个人的历史回顾的发现和主要概念的进展,导致我们目前的理解嘌呤信号。在该领域的主要人物的贡献得到承认。它包括嘌呤能神经肌肉和突触传递的发现,共传递,P1(腺苷),P2X核苷酸离子通道和P2Y核苷酸G蛋白偶联受体的鉴定,外核苷酸酶的鉴定,以及通过机械刺激和机械感觉转导从细胞释放ATP。它突出了哪些进步?它突出了嘌呤能信号传导的病理生理学和最近的治疗进展。这堂课是关于嘌呤能信号概念的历史。首先参考了Paton & Vane发表于的论文,该论文发现了几个物种对迷走神经刺激的非胆碱能放松反应,尽管他们认为这可能是由于迷走神经干中的交感肾上腺素能神经引起的。利用蔗糖间隙技术同时记录平滑肌的机械和电(在国家医学研究所Feldberg的部门开发的)豚鼠结肠带制剂(在Edith Bülbring在牛津药理学的平滑肌实验室工作时学到的),我们表明,在经典自主神经递质拮抗剂存在的情况下记录的超极化,乙酰胆碱和去甲肾上腺素是响应于非肾上腺素能、非胆碱能神经传递的抑制性连接电位,由迷走神经和骶副交感神经控制的肠内神经介导。然后,我们表明ATP满足识别这些神经释放的神经递质所需的标准。随后,研究表明ATP是外周和中枢神经系统中所有神经的共递质。嘌呤和嘧啶的受体在20世纪90年代初被克隆和鉴定,免疫染色显示大多数非神经元细胞以及神经细胞表达这些受体。嘌呤能信号的生理和病理生理进行了讨论。
What is the topic of this review? This is a personal historical review about the discovery and the main conceptual advances leading to our current understanding of purinergic signalling. The contributions of leading figures in the field are acknowledged. It includes the discovery of purinergic neuromuscular and synaptic transmission, cotransmission, the identification of P1 (adenosine), P2X nucleotide ion channel and P2Y nucleotide G protein-coupled receptors, the identity of ectonucleotidases and release of ATP from cells by mechanical stimulation and mechanosensory transduction. What advances does it highlight? It highlights the pathophysiology of purinergic signalling and recent therapeutic developments. This lecture is about the history of the purinergic signalling concept. It begins with reference to the paper by Paton & Vane published in, which identified non-cholinergic relaxation in response to vagal nerve stimulation in several species, although they suggested that it might be due to sympathetic adrenergic nerves in the vagal nerve trunk. Using the sucrose gap technique for simultaneous mechanical and electrical recordings in smooth muscle (developed while in Feldberg’s department in the National Institute for Medical Research) of the guinea-pig taenia coli preparation (learned when working in Edith Bülbring’s smooth muscle laboratory in Oxford Pharmacology), we showed that the hyperpolarizations recorded in the presence of antagonists to the classical autonomic neurotransmitters, acetylcholine and noradrenaline, were inhibitory junction potentials in response to non-adrenergic, non-cholinergic neurotransmission, mediated by intrinsic enteric nerves controlled by vagal and sacral parasympathetic nerves. We then showed that ATP satisfied the criteria needed to identify a neurotransmitter released by these nerves. Subsequently, it was shown that ATP is a cotransmitter in all nerves in the peripheral and central nervous systems. The receptors for purines and pyrimidines were cloned and characterized in the early 1990s, and immunostaining showed that most non-neuronal cells as well as nerve cells expressed these receptors. The physiology and pathophysiology of purinergic signalling is discussed.
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