2-APB is a nonspecific antagonist of calcium channels, commonly used in studies of calcium signaling, such as in apoptosis, muscle contraction, and neural transmission. It is a membrane-permeable inhibitor of the inositol-1,4,5-trisphosphate (InsP3) sensitive Ca2+ channels, with an IC50 value of 42μM when the concentration of InsP3 is 100nm[1]. Additionally, 2-APB has been found to affect the activity of TRP channels at certain concentrations [2].
In vitro, 2-APB can inhibit the increase in intracellular Ca2+ induced by thrombin in human platelets and neutrophils, as well as angiotensin II (AII)-induced contraction of the thoracic aorta [1]. In HEK-293 cells, 2-APB blocks the TRPC5 channel with an IC50 value of 20 μM [3]. In mouse pancreatic acinar cells, low concentrations of 2-APB significantly inhibit calcium store-operated calcium influx, while high concentrations inhibit direct stimulation-induced Ca2+ release and InsP3-induced Ca2+ release [4].
In vivo, when 2-APB is administered intravenously at 10 mg/kg to mice in an I/R model, it significantly reduces the infarct size, accompanied by a reduction in ROS levels and neutrophil infiltration, demonstrating potential cardioprotective effects [5]. Additionally, in I/R rats, 2-APB significantly increases superoxide dismutase (SOD), total antioxidant capacity (TAC), and glutathione (GSH), while reducing malondialdehyde (MDA) and DNA fragmentation, indicating that 2-APB has anti-apoptotic and antioxidative effects [6].
References:
[1]. Maruyama T, Kanaji T, Nakade S, et al. 2APB, 2-aminoethoxydiphenyl borate, a membrane-penetrable modulator of Ins(1,4,5)P3-induced Ca2+ release. J Biochem, 1997, 122(3): 498-505..
[2]. Togashi K , Inada H , Tominaga M .Inhibition of the transient receptor potential cation channel TRPM2 by 2-aminoethoxydiphenyl borate (2-APB)[J].British Journal of Pharmacology, 2008.
[3].Xu SZ, Zeng F, Boulay G, et al. Block of TRPC5 channels by 2-aminoethoxydiphenyl borate: a differential, extracellular and voltage-dependent effect. Br J Pharmacol, 2005, 145(4): 405-414.
[4]. Choi KJ, Kim KS, Kim SH, et al. Caffeine and 2-Aminoethoxydiphenyl Borate (2-APB) Have Different Ability to Inhibit Intracellular Calcium Mobilization in Pancreatic Acinar Cell. Korean J Physiol Pharmacol, 2010, 14(2): 105-111.
[5]. Hirofumi M , Masanori O , Shota T ,et al.2-aminoethoxydiphenyl borate provides an anti-oxidative effect and mediates cardioprotection during ischemia reperfusion in mice[J].Plos One, 2017, 12(12).
[6]. Sari E, Aksit H, Erken HA, et al. Protective effect of 2-APB on testicular ischemia-reperfusion injury in rats. J Urol, 2015, 193(3): 1036-1041.
2-APB是一种钙离子通道的非特异性拮抗剂，通常被用于研究钙信号传导，如细胞凋亡、肌肉收缩和神经传导等方面。2-APB是肌醇-1，4，5-三磷酸（InsP3）敏感性Ca2+通道的膜渗透性抑制剂，InsP3浓度为100 nm时，其IC50值为42μM[1]。此外，2-APB还被发现在一定浓度下能够影响TRP通道的活性[2]。
在体外，2-APB可以抑制凝血酶诱导的人类血小板和中性粒细胞胞内Ca2+增加，血管紧张素Ⅱ（AⅡ）诱导的胸主动脉收缩[1]。在HEK-293细胞中，2-APB阻断TRPC5通道，其IC50值为20 μM [3]。在小鼠胰腺腺泡细胞中，低浓度的2-APB可以显著抑制钙库调控的钙内流，高浓度的2-APB抑制直接刺激的Ca2+释放和InsP3诱导的Ca2+释放[4]。
在体内，2-APB以10 mg/kg静脉注射给予I/R模型小鼠时，2-APB能够显著减小梗塞面积，同时伴随着 ROS 水平和中性粒细胞浸润的减少，展现出潜在的心脏保护作用[5]。另外，在I/R大鼠中，2-APB显著增加超氧化物歧化酶（SOD）、总抗氧化能力（TAC）和谷胱甘肽（GSH），同时减少丙二醛（MDA）和DNA片段，2-APB具有抗凋亡和抗氧化作用[6]。