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.