CGP 42112 is an effective angiotensin II subtype 2 receptor (AT2R) agonist [1]. AT2R plays a crucial role in the development of the kidney and exerts anti-proliferative, anti-fibrotic and pro-apoptotic effects in vivo [2]. CGP 42112 can be used for studies on isolated rat hearts and vascular endothelial function [3].
In vitro, treatment of NR8383 cells with CGP 42112 (2nM) for 6-24 hours can weaken the effect of lipopolysaccharide (LPS) on the cells, significantly reduce the expression of M1 polarization markers (including iNOS and TNF-α), and inhibit the expression of p-p65, p50, p-ERK1/2 and p-IκBα [4]. CGP 42112 (0.1-100μM) treated the renal proximal tubule suspension (1mg/ml) at 37°C for 30 minutes can inhibit NKA activity in a dose-dependent manner and increase the accumulation of cGMP in the proximal tubules [5].
In vivo, CGP 42112 (5, 10 and 20μg/kg, once every 3 days, total three times) administered by intra-articular injection to rats can significantly reduce the arthritis index of a single left hind paw. CGP 42112 can improve the histological signs of arthritis rats [6]. CGP 42112 (1mg/kg; once; i.p.) administered to ATla-deficient mice has no effect on the plasma aldosterone and corticosterone levels of the mice [7].
References:
[1] Takekoshi K, Ishii K, Isobe K, et al. Angiotensin-II subtype 2 receptor agonist (CGP-42112) inhibits catecholamine biosynthesis in cultured porcine adrenal medullary chromaffin cells[J]. Biochemical and Biophysical Research Communications, 2000, 272(2): 544-550.
[2] Elbaz N, Bedecs K, Masson M, et al. Functional trans-inactivation of insulin receptor kinase by growth-inhibitory angiotensin II AT2 receptor[J]. Molecular Endocrinology, 2000, 14(6): 795-804.
[3] Raffai G, Durand M J, Lombard J H. Acute and chronic angiotensin-(1–7) restores vasodilation and reduces oxidative stress in mesenteric arteries of salt-fed rats[J]. American Journal of Physiology-Heart and Circulatory Physiology, 2011, 301(4): H1341-H1352.
[4] Zheng X, Xu Z, Xu L, et al. Angiotensin II Type 2 receptor inhibits M1 polarization and apoptosis of alveolar macrophage and protects against mechanical ventilation-induced lung injury[J]. Inflammation, 2025, 48(1): 165-180.
[5] Hakam A C, Hussain T. Angiotensin II AT2 receptors inhibit proximal tubular Na+-K+-ATPase activity via a NO/cGMP-dependent pathway[J]. American Journal of Physiology-Renal Physiology, 2006, 290(6): F1430-F1436.
[6] Wang D, Hu S, Zhu J, et al. Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant‐induced arthritis[J]. Journal of cellular and molecular medicine, 2013, 17(12): 1577-1587.
[7] Naruse M, Tanabe A, Sugaya T, et al. Deferential roles of angiotensin receptor subtypes in adrenocortical function in mice[J]. Life sciences, 1998, 63(18): 1593-1598.
CGP 42112是一种有效的血管紧张素II亚型2受体（AT2R）激动剂 [1]。AT2R在肾脏的发育过程中起着关键作用，并在体内发挥着抗增殖、抗纤维化和促凋亡的作用 [2]。CGP 42112可用于对大鼠离体心脏以及血管内皮功能的研究 [3]。
在体外，CGP 42112（2nM）处理NR8383细胞6-24h，能够减弱脂多糖（LPS ）对细胞的作用，显著降低了M1极化标志物（包括iNOS和TNF-α）的表达，同时抑制p-p65、p50、p-ERK1/2和p-IκBα的表达 [4]。CGP 42112（0.1-100M）在37℃下处理肾近端小管悬液（1mg/ml）30min，能够以剂量依赖性方式抑制NKA活性，增加近端小管中cGMP的蓄积[5]。
在体内， CGP 42112（5, 10和20μg/kg，每三天一次，总共三次）通过关节内注射治疗大鼠，能够显著降低单个左后爪的关节炎指数。CGP 42112可改善关节炎大鼠的组织学体征[6]。CGP 42112（1mg/kg; once; i.p.）注射ATla缺陷型小鼠后，对小鼠的血浆醛固酮和皮质酮水平没有影响[7]。