CCPA (2-Chloro-N6-cyclopentyladenosine) is a highly selective agonist for the A1 adenosine receptor (A1R; Kᵢ=0.4nM) and is commonly used to investigate physiological functions and signaling mechanisms mediated by the A1 receptor[1]. By activating the A1 receptor and inhibiting adenylate cyclase activity, CCPA reduces intracellular cyclic adenosine monophosphate (cAMP) levels, thereby modulating cardiac, neural, and metabolic systems[2-3]. CCPA has also been applied in exploring potential therapeutic strategies for diseases such as pulmonary fibrosis[4].
In vitro, pretreatment of SKBR-3 cells with CCPA (30μM) for 30 minutes, followed by co-incubation with GTP (50μM) for 72 hours, significantly inhibited GTP-induced cell death and increased cell viability[5]. Pretreatment of neonatal rat cardiomyocytes with CCPA (0.01–1μM) for 30 minutes prior to stimulation with angiotensin II (Ang II; 0.1μM) for 48 hours markedly suppressed Ang II-induced cardiomyocyte hypertrophy[6].
In vivo, daily intraperitoneal administration of CCPA (0.1mg/kg) to CD-1 mice subjected to a multiple-low-dose streptozotocin (40mg/kg) regimen over five consecutive days significantly reduced hyperglycemia in a model of type 1 diabetes[7]. A single intraperitoneal injection of CCPA (0.5 or 1mg/kg) in Wistar rats significantly altered the threshold and duration of hippocampal afterdischarges, demonstrating anticonvulsant effects[8].
References:
[1] Lohse MJ, Klotz KN, Schwabe U, et al. 2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1988 Jun;337(6):687-9.
[2] Concas A, Santoro G, Mascia MP, et al. Anticonvulsant doses of 2-chloro-N6-cyclopentyladenosine, an adenosine A1 receptor agonist, reduce GABAergic transmission in different areas of the mouse brain. J Pharmacol Exp Ther. 1993 Nov;267(2):844-51.
[3] Concas A, Cuccheddu T, Floris S, et al. 2-Chloro-N6-cyclopentyladenosine (CCPA), an adenosine A1 receptor agonist, suppresses ethanol withdrawal syndrome in rats. Alcohol Alcohol. 1994 May;29(3):261-4.
[4] Della Latta V, Cabiati M, Rocchiccioli S, et al. The role of the adenosinergic system in lung fibrosis. Pharmacol Res. 2013 Oct;76:182-9.
[5] Hotani A, Kitabatake K, Tsukimoto M. Extracellular Guanosine and Guanine Nucleotides Decrease Viability of Human Breast Cancer SKBR-3 Cells. Biol Pharm Bull. 2024 Jan 1;47(1):14-22.
[6] Zhang X, Xia J, Qian D, et al. An adenosine A1 agonist 2-chloro-N6 cyclopentyladenosine inhibits the angiotensin II-induced cardiomyocyte hypertrophy through the calcineurin pathway. Cardiology. 2014;129(3):153-62.
[7] Németh ZH, Bleich D, Csóka B, et al. Adenosine receptor activation ameliorates type 1 diabetes. FASEB J. 2007 Aug;21(10):2379-88.
[8] Fabera P, Parizkova M, Uttl L, et al. Adenosine A1 Receptor Agonist 2-chloro-N6-cyclopentyladenosine and Hippocampal Excitability During Brain Development in Rats. Front Pharmacol. 2019 Jun 14;10:656.