DPCPX is a potent and selective high affinity A1 adenosine receptor antagonist with a Ki value of 0.45nM for adenylate cyclase in rat fat cell membranes [1]. The A1 adenosine receptor is an important G protein-coupled receptor whose activation inhibits adenylyl cyclase activity, regulates calcium ion channels, and inhibits potassium ion channels, thereby modulating cardiac function, neurotransmission, and various physiological processes[2]. DPCPX is a xanthine analog that competitively binds to the adenosine binding site on the A1 adenosine receptor, inhibiting its activation. It is commonly used to study the function of A1 adenosine receptors and their roles in cardiovascular, neurological, metabolic systems, and certain cancers[1,3].
DPCPX is used to evaluate pharmacological differences in A1 adenosine receptors from different sources. [3H]-DPCPX was used to treat the membranes of human, guinea pig, rat, and mouse brains (treatment concentrations and times were: human: 0.7nM, 120min; guinea pig: 0.2nM, 60min; rat and mouse: 0.1nM, 20min). DPCPX exhibited significant differences in binding properties to membranes from different species, while maintaining relatively consistent binding affinity across different brain regions within the same species[4]. Treatment of MCF-7 cells with DPCPX (87nM) for 24, 48, and 72h resulted in increased expression of p53, caspase 3, 8, and 9, and a decrease in cell viability, indicating that DPCPX promotes apoptosis in MCF-7 cells[5].
DPCPX (1mg/kg) administered intraperitoneally to mice significantly reduced renal damage caused by the radiocontrast agent iohexol[6]. DPCPX (0.25mg/kg) administered subcutaneously to rats significantly increased the mortality rate, neurological deficit scores, and brain infarction volume in middle cerebral artery occlusion (MCAO) rats, while reducing the neuroprotective effects of tetramethylpyrazine (TSG) [7].
References:
[1] Lohse M, Klotz K N, Lindenborn-Fotinos J, et al., 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) — a selective high affinity antagonist radioligand for A1 adenosine receptors, Naunyn-Schmiedeberg's archives of pharmacology[J]. 1987, 336: 204-210.
[2] Linden J, Structure and function of A1 adenosine receptors, FASEB journal : official publication of the Federation of American Societies for Experimental Biology[J]. 1991,12: 2668-76.
[3] Moro S, Gao Z G, Jacobson K A, et al., Progress in the pursuit of therapeutic adenosine receptor antagonists, Medicinal Research Reviews[J]. 2005, 26: 131-159.
[4] Maemoto T, Finlayson K, Olverman H J, Akahane A, et al., Species differences in brain adenosine A1 receptor pharmacology revealed by use of xanthine and pyrazolopyridine based antagonists, British Journal of Pharmacology[J]. 1997, 122: 1202-1208.
[5] Dastjerdi M N, Rarani M Z, Valiani A, et al., The effect of adenosine A1 receptor agonist and antagonist on p53 and caspase 3, 8, and 9 expression and apoptosis rate in MCF-7 breast cancer cell line, Research in Pharmaceutical Sciences[J]. 2016, 11: 303-310.
[6] Lee H T, Jan M, Bae S C, et al., A1 adenosine receptor knockout mice are protected against acute radiocontrast nephropathy in vivo, American Journal of Physiology-Renal Physiology[J]. 2006, 290: F1367-F1375.
[7] Ruan L, Li G, Zhao W, et al., Activation of Adenosine A1 Receptor in Ischemic Stroke: Neuroprotection by Tetrahydroxy Stilbene Glycoside as an Agonist, Antioxidants[J]. 2021, 10: 1112.
DPCPX 是一种高效、选择性强且具有高亲和力的 A1 腺苷受体拮抗剂，对大鼠细胞膜腺苷酸环化酶的 Ki 值为 0.45 nM[1]。A1 腺苷受体是一种重要的G蛋白偶联受体，其激活能抑制腺苷酸酰化酶的活性，调节钙离子通道，抑制钾离子通道，从而调节心脏功能、神经传递等多种生理过程[2]。DPCPX是一种黄嘌呤类似物，能够和A1 腺苷受体上的腺苷结合位点竞争性结合，从而抑制A1 腺苷受体的激活，常用于研究 A1 腺苷受体的功能及其在心血管、神经、代谢以及部分癌症等系统中的作用[1,3]。
DPCPX 用于评估不同来源的A1腺苷受体的药理特性差异。用[3H]-DPCPX对人类、豚鼠、大鼠和小鼠的脑膜进行处理（DPCPX的处理浓度以及处理时间分别为：人类：0.7 nM，120min；豚鼠：0.2nM，60min；大鼠和小鼠：0.1nM，20min），发现DPCPX对不同物种的膜的结合特性存在显著差异，但对同一物种的不同脑区的膜的结合亲和力相对一致[4]。DPCPX（87nM）处理MCF-7细胞24h、48h以及72h，相对于未处理的细胞，其p53及caspase 3、8、9的表达增多，细胞存活率下降，表明DPCPX 能够促进MCF-7细胞的凋亡[5]。
DPCPX（1mg/kg）通过腹腔注射的方式对小鼠进行处理，能够显著减少放射性对比剂碘苯六醇对小鼠肾功能的损伤[6]。DPCPX（0.25mg/kg）通过皮下注射的方式对大鼠进行处理，能够显著增加中大脑动脉闭塞（MCAO）大鼠的死亡率、神经行为缺陷评分和脑梗死体积，降低四羟基苯乙烯苷（TSG）对神经的保护作用[7]。