Geoffrey Burnstock made a chance observation early in his research career that did not fit the conventional scientific dogma—non-noradrenergic, non-cholinergic (NANC) nerves. Instead of rejecting these as an artifact, he followed their logical course to characterize the actions of extracellular ATP on nerves and muscles, eventually founding a large branch of pharmacology around purinergic signaling. The solid proof that validated his concept and dismissed many detractors was the cloning of seven ionotropic P2X receptors and eight metabotropic P2Y receptors, which are expressed in some combination in every tissue and organ. Given the broad importance of this signaling system in biology, medicinal chemists, inspired by Burnstock, began creating synthetic agonists and antagonists for these purinergic receptors. Various ligands have advanced to clinical trials, for disorders of the immune, nervous, cardiovascular, and other systems, and a few are already approved. Thus, medically important approaches have been derived from Burnstock’s original pharmacological concepts and his constant guiding of the course of the field. The therapeutic potential of modulators of purinergic signaling is vast.

杰弗里·伯恩斯托克 (Geoffrey Burnstock) 在他的研究生涯早期进行了一次偶然的观察，该观察不符合传统的科学教条——非去甲肾上腺素能、非胆碱能 (NANC) 神经。他没有拒绝将这些视为人工制品，而是按照他们的逻辑过程来表征细胞外 ATP 对神经和肌肉的作用，最终围绕嘌呤能信号建立了一个大的药理学分支。证实他的概念并驳回许多批评者的确凿证据是克隆了 7 种离子型 P2X 受体和 8 种代谢型 P2Y 受体，它们在每个组织和器官中以某种组合表达。鉴于此信号系统在生物学中的广泛重要性，药物化学家在 Burnstock 的启发下，开始为这些嘌呤能受体创造合成激动剂和拮抗剂。各种配体已进入临床试验，用于治疗免疫、神经、心血管和其他系统的疾病，其中一些已经获得批准。因此，医学上重要的方法源自 Burnstock 的原始药理学概念和他对该领域进程的持续指导。嘌呤信号调节剂的治疗潜力是巨大的。