Department of Pharmacological and Biomolecular Sciences, School of Pharmacy, Universita degli Studi di Milano, Milan, Italy.
SMI, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
Curr Med Chem. 2018;25(32):3830-3865. doi: 10.2174/0929867324666170710110630.
The purinergic system is composed of purine and pyrimidine transmitters, the enzymes that modulate the interconversion of nucleotides and nucleosides, the membrane transporters that control their extracellular concentrations, and the many receptor subtypes that are responsible for their cellular responses. The components of this system are ubiquitously localized in all tissues and organs, and their involvement in several physiological conditions has been clearly demonstrated. Moreover, extracellular purine and pyrimidine concentrations rise several folds under pathological conditions like tissue damage, ischemia, and inflammation, which suggest that this signaling system might contribute both to disease outcome and, possibly, to its tentative resolution. The complexity of this system has greatly impaired the clear identification of the mediators and receptors that are actually involved in a given pathology, also due to the often opposite roles played by the various receptor subtypes. Nevertheless, this knowledge is fundamental for the possible exploitation of these molecular entities as targets for the development of new pharmacological approaches. In this review, we aim at highlighting what is currently known on the role of the purinergic system in various pain conditions and during inflammatory processes. Although some confusion may arise from conflicting results, literature data clearly show that targeting specific purinergic receptors may represent an innovative approach to various pain and inflammatory conditions, and that new purine-based drugs are now very close to reach the market with these indications.
嘌呤能系统由嘌呤和嘧啶递质、调节核苷酸和核苷相互转化的酶、控制其细胞外浓度的膜转运体以及负责细胞反应的许多受体亚型组成。该系统的组成部分在所有组织和器官中广泛存在，其在多种生理条件下的参与已得到明确证实。此外，在组织损伤、缺血和炎症等病理条件下，细胞外嘌呤和嘧啶浓度会升高数倍，这表明该信号系统可能既有助于疾病的结果，也可能有助于疾病的尝试性解决。该系统的复杂性极大地阻碍了对实际参与特定病理学的介质和受体的明确识别，这也是由于各种受体亚型经常发挥相反的作用。然而，这些知识对于将这些分子实体作为开发新的药理学方法的靶点的可能性是至关重要的。在这篇综述中，我们旨在强调嘌呤能系统在各种疼痛状况和炎症过程中的作用。尽管可能会因相互矛盾的结果而产生一些混淆，但文献数据清楚地表明，针对特定的嘌呤能受体可能是治疗各种疼痛和炎症状况的一种创新方法，并且基于新嘌呤的药物现在非常接近这些适应症进入市场。
