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.