Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, Chodźki 1, PL 20-093 Lublin, Poland.
Department of Animal Physiology and Pharmacology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, PL 20-033 Lublin, Poland.
Pharmacol Ther. 2021 Aug;224:107821. doi: 10.1016/j.pharmthera.2021.107821. Epub 2021 Feb 17.
Purinergic signaling involves the actions of purine nucleotides and nucleosides (such as adenosine) at P1 (adenosine), P2X, and P2Y receptors. Here, we present recent data contributing to a comprehensive overview of the association between purinergic signaling and depression. We start with background information on adenosine production and metabolism, followed by a detailed characterization of P1 and P2 receptors, with an emphasis on their expression and function in the brain as well as on their ligands. We provide data suggestive of altered metabolism of adenosine in depressed patients, which might be regarded as a disease biomarker. We then turn to considerable amount of preclinical/behavioral data obtained with the aid of the forced swim test, tail suspension test, learned helplessness model, or unpredictable chronic mild stress model and genetic activation/inactivation of P1 or P2 receptors as well as nonselective or selective ligands of P1 or P2 receptors. We also aimed to discuss the reason underlying discrepancies observed in such studies.
嘌呤能信号涉及嘌呤核苷酸和核苷（如腺苷）在 P1（腺苷）、P2X 和 P2Y 受体上的作用。在这里，我们呈现了最近的数据，这些数据有助于全面了解嘌呤能信号与抑郁症之间的关联。我们首先介绍了关于腺苷产生和代谢的背景信息，然后详细描述了 P1 和 P2 受体，重点介绍了它们在大脑中的表达和功能以及它们的配体。我们提供的数据表明抑郁症患者腺苷代谢发生改变，这可能被视为疾病生物标志物。然后，我们转向大量的临床前/行为学数据，这些数据是借助强迫游泳试验、悬尾试验、习得性无助模型或不可预测的慢性轻度应激模型以及 P1 或 P2 受体的基因激活/失活以及 P1 或 P2 受体的非选择性或选择性配体获得的。我们还旨在讨论在这些研究中观察到的差异的原因。
