Burnstock Geoffrey
Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, VIC, Australia.
Methods Mol Biol. 2020;2041:1-15. doi: 10.1007/978-1-4939-9717-6_1.
Purinergic signaling was proposed in 1972, after it was demonstrated that adenosine 5'-triphosphate (ATP) was a transmitter in nonadrenergic, noncholinergic inhibitory nerves supplying the guinea-pig taenia coli. Later, ATP was identified as an excitatory cotransmitter in sympathetic and parasympathetic nerves, and it is now apparent that ATP acts as a cotransmitter in most, if not all, nerves in both the peripheral nervous system and central nervous system (CNS). ATP acts as a short-term signaling molecule in neurotransmission, neuromodulation, and neurosecretion. It also has potent, long-term (trophic) roles in cell proliferation, differentiation, and death in development and regeneration. Receptors to purines and pyrimidines have been cloned and characterized: P1 adenosine receptors (with four subtypes), P2X ionotropic nucleotide receptors (seven subtypes) and P2Y metabotropic nucleotide receptors (eight subtypes). ATP is released from different cell types by mechanical deformation, and after release, it is rapidly broken down by ectonucleotidases. Purinergic receptors were expressed early in evolution and are widely distributed on many different nonneuronal cell types as well as neurons. Purinergic signaling is involved in embryonic development and in the activities of stem cells. There is a growing understanding about the pathophysiology of purinergic signaling and there are therapeutic developments for a variety of diseases, including stroke and thrombosis, osteoporosis, pain, chronic cough, kidney failure, bladder incontinence, cystic fibrosis, dry eye, cancer, and disorders of the CNS, including Alzheimer's, Parkinson's. and Huntington's disease, multiple sclerosis, epilepsy, migraine, and neuropsychiatric and mood disorders.
1972年，有研究证明5'-三磷酸腺苷（ATP）是供应豚鼠结肠带的非肾上腺素能、非胆碱能抑制性神经中的一种递质，之后嘌呤能信号传导被提出。后来，ATP被确定为交感神经和副交感神经中的一种兴奋性共递质，现在很明显，ATP在周围神经系统和中枢神经系统（CNS）的大多数（如果不是全部）神经中都作为共递质起作用。ATP在神经传递、神经调节和神经分泌中作为一种短期信号分子发挥作用。它在发育和再生过程中的细胞增殖、分化和死亡中也具有强大的长期（营养）作用。嘌呤和嘧啶的受体已被克隆和鉴定：P1腺苷受体（有四种亚型）、P2X离子型核苷酸受体（七种亚型）和P2Y代谢型核苷酸受体（八种亚型）。ATP通过机械变形从不同细胞类型中释放出来，释放后，它会被外核苷酸酶迅速分解。嘌呤能受体在进化早期就已表达，广泛分布于许多不同的非神经元细胞类型以及神经元上。嘌呤能信号传导参与胚胎发育和干细胞的活动。人们对嘌呤能信号传导的病理生理学有了越来越多的了解，并且针对多种疾病有了治疗进展，包括中风和血栓形成、骨质疏松症、疼痛、慢性咳嗽、肾衰竭、膀胱失禁、囊性纤维化、干眼症、癌症以及中枢神经系统疾病，包括阿尔茨海默病、帕金森病、亨廷顿舞蹈病、多发性硬化症、癫痫、偏头痛以及神经精神和情绪障碍。
