Florenzano F, Viscomi M T, Amadio S, D'Ambrosi N, Volonté C, Molinari M
Experimental Neurorehabilitation Laboratory, I.R.C.C.S. Santa Lucia Foundation, Via del Fosso di Fiorano 65, 00143 Rome, Italy.
Prog Neurobiol. 2008 Jan;84(1):40-56. doi: 10.1016/j.pneurobio.2007.10.004. Epub 2007 Oct 18.
Enzymatically derived NO and extracellular ATP are receiving greater attention due to their role as messengers in the CNS during different physiological and pathological processes. Ionotropic (P2XR) and metabotropic (P2YR) purinergic receptors mediate ATP effects and are present throughout the body. Particularly P2XR are crucial for brain plasticity mechanisms, and are involved in the pathogenesis of different CNS illnesses. NO does not have a specific receptor and its actions are directly dependent on the production on demand by different nitric oxide synthase isoforms. NO synthesizing enzymes are present virtually in all tissues, and NO influences multifarious physiological and pathological functions. Interestingly, various are the tissue and organs modulated by both ATP and NO, such as the immune, brain and vascular systems. Moreover, direct interactions between purinergic and nitrergic mechanisms outside the CNS are well documented, with several studies also indicating that ATP and NO do participate to the same CNS functions. In the past few years, further experimental evidence supported the physiological and pathological relevance of ATP and NO direct interactions in the CNS. The aim of the present review is to provide an account of the available information on the interplay between purinergic and nitrergic systems, focussing on the CNS. The already established relevance of ATP and NO in different pathological processes would predict that the knowledge of ATP/NO cross-talk mechanisms would support pharmacological approaches toward the development of novel ATP/NO combined pharmacological agents.
酶促产生的一氧化氮（NO）和细胞外ATP作为中枢神经系统（CNS）在不同生理和病理过程中的信使，正受到越来越多的关注。离子型（P2XR）和代谢型（P2YR）嘌呤能受体介导ATP的作用，遍布全身。特别是P2XR对脑可塑性机制至关重要，并参与不同中枢神经系统疾病的发病过程。NO没有特定的受体，其作用直接取决于不同一氧化氮合酶同工型按需产生的情况。NO合成酶几乎存在于所有组织中，NO影响多种生理和病理功能。有趣的是，ATP和NO共同调节的组织和器官多种多样，如免疫、脑和血管系统。此外，中枢神经系统外嘌呤能和一氧化氮能机制之间的直接相互作用已有充分记录，多项研究还表明ATP和NO确实参与相同的中枢神经系统功能。在过去几年中，更多实验证据支持了ATP和NO在中枢神经系统中直接相互作用的生理和病理相关性。本综述的目的是介绍有关嘌呤能和一氧化氮能系统相互作用的现有信息，重点是中枢神经系统。ATP和NO在不同病理过程中已确立的相关性预示着，了解ATP/NO相互作用机制将有助于开发新型ATP/NO联合药物的药理学方法。
