A-779 (trifluoroacetate salt)

A-779 is a peptide antagonist of the Mas receptor, also known as the angiotensin (1-7) (Ang (1-7)) receptor (IC₅₀ = 0.3 nM in a radioligand binding assay).¹ It does not compete with angiotensin 1 (AT₁) and AT₂ receptor agonists for binding in adrenocortical membranes when used at a concentration of 1 µM and exhibits an IC₅₀ value greater than 10 µM in adrenomedullary membranes.² In vitro, A-779 inhibits Ang (1-7)-induced release of arachidonic acid from CHO cells transfected with Mas.¹ A-779 (0.01 mg/kg) prevents the antidiuretic effects of Ang (1-7) in water-loaded rats. It also inhibits the Ang (1-7)-induced decrease in mean arterial pressure (MAP) when administered by microinjection into the nucleus of the solitary tract with no effect on basal MAP. A-779 increases urine flow rate and sodium excretion in male, but not female, rats when AT₁ and AT₂ receptors are blocked by the selective antagonists losartan and PD 123319 , respectively.³

1.Santos, R.A., Simoes e Silva, A.C., Maric, C., et al.Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor MasProc. Natl. Acad. Sci. U.S.A.100(14)8258-8263(2003) 2.Santos, R.A., Campagnole-Santos, M.J., Baracho, N.C., et al.Characterization of a new angiotensin antagonist selective for angiotensin-(1-7): Evidence that the actions of angiotensin-(1-7) are mediated by specific angiotensin receptorsBrain Res. Bull.35(4)293-298(1994) 3.Mansoori, A.O., S., and Nematbakhsh, M.Role of Mas receptor antagonist (A779) on pressure diuresis and natriuresis and renal blood flow in the absence of angiotensin II receptors type 1 and 2 in female and male ratsJ. Physiol. Pharmacol.65(5)633-639(2014)