EIPA inhibited TRPP3-mediated Ca2+-activated currents with IC50 values of 10.5 μM [1]. TRPP3, a member of the transient receptor potential (TRP) superfamily of cation channels, is a Ca2+-activated channel permeable to Ca2+, Na+, and K+ [1].EIPA (5-(N-ethyl-N-isopropyl)-amiloride) is a commonly used amiloride derivative modified similarly to MPA, and its Ki for NHE1, NHE2, and NHE3 are 0.3, 1.8, and 67 μM, respectively[2,3]
EIPA suppressed proliferation of MKN28 cells through up-regulation of p21 expression via reduction of [Cl- ] c as a result from DIDS-sensitive Cl- /HCO3- exchanger-mediated compensation for keeping pHc normal under an NHE-inhibited condition [4].
EIPA preischemic treatment overcame the I/R-induced renal dysfunction. Histologic examination of the kidney of vehicle-treated ARF mice revealed severe lesions, and these lesions were significantly suppressed by the preischemic treatment with EIPA. In addition, EIPA suppressed the increment of renal ET-1 content after reperfusion [5]. EIPA at doses of 3 and 9 mg/kg per day inhibited tumor growth of HepG2 modle mice significantly compared with the control [6].
References:
[1]. Dai XQ, Ramji A, Liu Y, Li Q, Karpinski E, Chen XZ (2007) Inhibition of TRPP3 channel by amiloride and analogs. Mol Pharmacol 72:1576-1585
[2]. Guffey, S.C.; Fliegel, L.; Goss, G.G. Cloning and characterization Na+/H+ Exchanger isoforms, NHE2 and, NHE3 from the gill Pacific dogfish, Squalus suckleyi. Comp. Biochem. Physiol. Part B Biochem. Mol. Biol. 2015, 188, 46-53.
[3]. Masereel, B. An overview inhibitors Na+/H+ exchanger. Eur. J. Med. Chem. 2003, 38, 547-554.
[4]. Hosogi SMH, Nakajima K, Ashihara E, Niisato N, Kusuzaki K, Marunaka Y: An inhibitor of Na(+)/H(+) exchanger (NHE), ethyl-isopropyl amiloride (EIPA), diminishes proliferation of MKN28 human gastric cancer cells by decreasing the cytosolic Cl(-) concentration via DIDS-sensitive pathways. Cell Physiol Biochem. 2012, 30: 1241-1253. 10.1159/000343315.
[5]. Yamashita J, Ohkita M, Takaoka M, Kaneshiro Y, Matsuo T,Kaneko K, Matsumura Y.Role of Na+/H+ exchanger in the pathogen-esis of ischemic acute renal failure in mice.J Cardiovasc Pharmacol49:154 -160, 2007.
[6]. X. Yang, D. Wang, W. Dong, Z. Song, K. Dou.Expression and modulation of Na+/H+ exchanger 1 gene in hepatocellular carcinoma: a potential therapeutic target. J. Gastroenterol. Hepatol., 26 (2) (2011), pp. 364-370
EIPA 抑制 TRPP3 介导的 Ca2+- 激活电流，IC50 值为 10.5 μM [1]。 TRPP3 是阳离子通道瞬时受体电位 (TRP) 超家族的成员，是 Ca2+- 激活通道，可渗透 Ca2+、Na+ 和 K+ [1].EIPA (5-(N-ethyl-N -isopropyl)-amiloride)是一种常用的类似MPA修饰的阿米洛利衍生物，其对NHE1、NHE2和NHE3的Ki值分别为0.3、1.8和67 μM[2,3] /p>\n
EIPA 通过减少 [Cl-] c 上调 p21 表达来抑制 MKN28 细胞的增殖，这是由于 DIDS 敏感的 Cl- /HCO3- 交换剂介导的补偿，以在 NHE 抑制条件下保持 pHc 正常[4].
EIPA 缺血前治疗克服了 I/R 引起的肾功能障碍。载体治疗的 ARF 小鼠肾脏的组织学检查显示严重病变，并且这些病变被 EIPA 的缺血前治疗显着抑制。此外，EIPA抑制再灌注后肾脏ET-1含量的增加[5]。与对照组相比，每天 3 和 9 mg/kg 剂量的 EIPA 显着抑制 HepG2 模型小鼠的肿瘤生长[6]。
EIPA 通过减少 [Cl-] c 上调 p21 表达来抑制 MKN28 细胞的增殖，这是由于 DIDS 敏感的 Cl- /HCO3- 交换剂介导的补偿，以在 NHE 抑制条件下保持 pHc 正常[4].
EIPA 缺血前治疗克服了 I/R 引起的肾功能障碍。载体治疗的 ARF 小鼠肾脏的组织学检查显示严重病变，并且这些病变被 EIPA 的缺血前治疗显着抑制。此外，EIPA抑制再灌注后肾脏ET-1含量的增加[5]。与对照组相比，每天 3 和 9 mg/kg 剂量的 EIPA 显着抑制 HepG2 模型小鼠的肿瘤生长[6]。