Adenosine is an endogenous neuroregulatory substance, containing adenine, which is linked to the ribose molecule (furanose) through a β-N9-glycosidic bond [1]. Adenosine affects almost all aspects of cellular physiology, including neuronal activity, vascular function, platelet aggregation, and hematopoietic regulation. Adenosine can be used to treat supraventricular tachycardia [2].
In vitro, different concentrations of Adenosine (1.0-4.0mM; 12, 24 and 48 hours) inhibited the survival rate of HepG2 cells in a time- and dose-dependent manner, significantly increased the mRNA and protein levels of GRP78/BiP, PERK, ATF4, CHOP, caspase-3, and cytochrome c, reduced mitochondrial membrane potential, and activated endoplasmic reticulum stress [3]. Adenosine (0.5-4.0mM; 36 hours) significantly increased the expression of caspase-3 in EC109 cells in a dose-dependent manner, induce cell apoptosis and NF-κB activation [4].
In vivo, Adenosine (1-10mg/kg/day; i.p.) was administered as a single dose to mice in the forced swimming test (FST) and tail suspension test (TST), significantly shortening the immobility time in FST and producing a similar antidepressant-like effect in TST [5]. Adenosine (5mg/kg/day; i.p.; six times, at one-hour intervals) treatment in mice increased the expression level of the inflammatory reactive astrocyte marker (Lcn 2), and simultaneously enhanced the expression of several other pro-inflammatory cytokine/cytokine chemotactic factor genes, such as Ccl 2, Cxcl 1, Ilia and Tnf [6].
References:
[1] Fredholm B B, Chen J F, Cunha R A, et al. Adenosine and brain function[J]. Int Rev Neurobiol, 2005, 63(1): 191-270.
[2] Borea PA, Gessi S, Merighi S, et al. Pharmacology of Adenosine Receptors: The State of the Art. Physiol Rev. 2018 Jul 1;98(3):1591-1625.
[3] Zhou XT, Pu ZJ, Liu LX,,et al.. Inhibition of autophagy enhances adenosine‑induced apoptosis in human hepatoblastoma HepG2 cells. Oncol Rep. 2019 Feb;41(2):829-838.
[4] Wu L F, Wei B L, Guo Y T, et al. Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109 cells[J]. International journal of molecular medicine, 2012, 30(4): 797-804.
[5] Kaster MP, Rosa AO, Rosso MM, et al. Adenosine administration produces an antidepressant-like effect in mice: evidence for the involvement of A1 and A2A receptors. Neurosci Lett. 2004;355(1-2):21-24.
[6] Guo Q, Gobbo D, Zhao N, et al. Adenosine triggers early astrocyte reactivity that provokes microglial activation and drives the pathogenesis of sepsis-associated encephalopathy[J]. bioRxiv, 2023: 2023.10. 30.563169.
Adenosine是一种内源性神经调节物质，包含腺嘌呤，通过β-N9-糖苷键与核糖分子（呋喃核糖）部分连接 [1]。Adenosine几乎影响细胞生理学的所有方面，包括神经元活动、血管功能、血小板聚集和血细胞调节。Adenosine能够用于治疗室上性心动过速 [2]。
在体外，不同浓度的Adenosine（1.0-4.0mM; 12、24和48h）能够以时间和剂量依赖性方式抑制HepG 2细胞的存活率，显著升高GRP 78/BiP、PERK、ATF 4、CHOP、caspase-3、细胞色素c的mRNA和蛋白水平，降低线粒体膜电位，激活内质网应激 [3]。Adenosine（0.5-4.0mM; 36h）能够以剂量依赖性方式显著增加EC 109细胞caspase-3的表达，诱导细胞凋亡和NF-κB活化 [4]。
在体内，Adenosine（1-10mg/kg/day；i.p.）单次给药治疗强迫游泳试验（FST）和悬尾试验（TST）小鼠，显著缩短了FST中的不动时间，在TST中产生类似抗抑郁药的作用 [5]。Adenosine（5mg/kg/day；i.p.；六次，每次间隔一小时）治疗小鼠，上调了炎性反应性星形胶质细胞的标志物（Lcn 2）的表达水平，同时增加了几种其他促炎细胞因子/趋化因子基因，如Ccl 2、Cxcl 1、Illa和Tnf的表达 [6]。