| Bioactivity | A 779 is a specific antagonist of G-protein coupled receptor (Mas receptor), which is an Ang1-7 receptor distinct from the classical AngII. | ||||||
| Invitro | A-779 inhibits the effect of Ang-(1-7), which suppresses the proliferating cell nuclear antigen (PCNA) protein expression up-regulated by Ang II, but A-779 alone has no effect to induce proliferation and migration of VSMCs. Pretreatment with Ang-(1-7) significantly retards Ang II-induced inflammatory responses of VSMCs associated with up-regulated MCP-1, VCAM-1 and IL-1β expressions, and this effect of Ang-(1-7) is blocked by A-779. But A-779 alone has no effect to induce inflammatory response of VSMCs. Pretreatment VSMCs with Ang-(1-7) for 5 min significantly inhibits Akt and ERK1/2 phosphorylation induced by Ang II, and this effect is also blocked by A-779, but alone has no effect to induce phosphorylation of Akt and ERK1/2 in VSMCs[3]. | ||||||
| In Vivo | Infusion of Ang(1-7) and A-779 (400 ng/kg/min, s.c.) alone or combined for 6 weeks does not prevent uterus atrophy or inhibit the body weight gain of OVX rats. A-779 markedly elevates serum bone specific alkaline phosphatase (BALP), telopeptides of collagen type I (CTX), tartarate resistant acid phosphatase (TRAcP 5b), osteocalcin (OC) and urinary deoxypyridinoline (DPD). Infusion of Ang(1-7) and/or A-779 does not significantly change serum minerals concentrations in sham or OVX groups. A-779 in the OVX animals does not change AngII, Ang(1-7), AT1R, AT2R, ACE, ACE-2, Mas receptor, RANKL and OPG proteins expressions in relation to OVX group, while AngII (P < 0.05), AT1R (P < 0.05), ACE (P < 0.01) and RANKL (P < 0.01) expressions are significantly higher and Ang(1-7), AT2R, ACE-2, MasR and OPG are significantly (P < 0.01) lower than sham group. Blocking of the G-protein coupled receptor (Mas) by A-779 markedly abolishes Ang(1-7) favorable effects on bone health suggesting the vital role of Mas receptor in mediating Ang(1-7) osteo-protective effects[1]. Inhibition of Ang1-7 cascade by A-779 (400 ng/kg/min) significantly eradicates captopril protective effects on bone metabolism, mineralization and micro-structure. A-779 also restores OVX effects on RANKL expression and ACE-1/AngII/AT1R cascade and down-regulates OPG expression and ACE-2/Ang1-7/Mas pathway[2]. | ||||||
| Name | A 779 | ||||||
| CAS | 159432-28-7 | ||||||
| Sequence | Asp-Arg-Val-Tyr-Ile-His-{d-Ala} | ||||||
| Shortening | DRVYIH-{d-Ala} | ||||||
| Formula | C39H60N12O11 | ||||||
| Molar Mass | 872.97 | ||||||
| Appearance | Solid | ||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||
| Storage | Sealed storage, away from moisture
*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
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| Reference | [1]. Abuohashish HM, et al. Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis in rats via activation of ACE-2/Mas receptor axis. Sci Rep. 2017 May 23;7(1):2293. [2]. Abuohashish HM, et al. ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats. Biomed Pharmacother. 2017 Aug;92:58-68. [3]. Yan WF, et al. Effects and related mechanism of angiotensin-(1-7) on Toll-like receptor 4-mediated oxidative stress in human umbilical vein endothelial cells. Zhonghua Xin Xue Guan Bing Za Zhi. 2017 Mar 24;45(3):223-229. |