Angiotensin-(1–7) binding at angiotensin II receptors in the rat brain

Angiotensin-(1–7) (Ang-(1–7)) is reported to be equipotent with angiotensin II (AII) in producing some central biological effects but the receptors responsible for these actions have not been defined. Three classes of receptor have been proposed: AT 1, AT 2, and a putative Ang-(1–7) selective receptor. This study specifically evaluates Ang-(1–7) competition at AII binding sites (AT 1 and AT 2) in the rat brain. 125I Sar 1 Ile 8 AII (269–312 pM) was used to conduct receptor autoradiographic binding assays in brain sections. Competition with Ile 5 AII and Val 5 AII was similar at nuclei in which either AT 1 or AT 2 receptor subtypes predominate ( K i = 11–18 nM). Ang-(1–7) competed 150-fold less effectively than native AII at AT 1 predominant brain nuclei ( K i = 2.4 μM). At brain regions where AT 2 receptors predominate, Ang-(1–7) showed a very low affinity ( K i = 104 μM) for the majority of the 125I Sar 1 Ile 8 AII binding sites (AT 2). A small proportion of 125I Sar 1 Ile 3 AII binding sites showed an affinity of 2.0 μM, presumably AT 1 receptors present in those brain regions. For biological responses where Ang-(1–7) is reported to be equipotent with AII, it is unlikely that these actions are mediated by the widely distributed AT 1 or AT 2 receptor subtypes which recognize 125I Sar 1 Ile 8 AII.