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A 779

CAS No. : 159432-28-7

MCE 国际站：A 779

产品活性：A 779 是G蛋白偶联受体Mas的有效拮抗剂，Mas受体为一种Ang1-7 receptor，区别于传统的AngII。

研究领域：GPCR/G Protein

作用靶点：Angiotensin Receptor

In Vitro: 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.

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. 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.

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