IDENTIFICATION OF AN AII(3-8) [AIV] BINDING-SITE IN GUINEA-PIG HIPPOCAMPUS

A unique angiotensin binding site specific for the hexapeptide, AII(3-8), has been identified in guinea pig hippocampus. This binding site, which is present in the pyramidal cell layer of CA1, CA2, CA3 of the hippocampus and dentate gyrus, binds AII(3-8) with high affinity (K(D) = 1.29+/-0.18 nM) in a saturable manner (B(max) = 449+/-62 fmol/mg protein). The N-terminal structure of the binding ligand is paramount in determining the binding affinity. The C-terminal requirements seem less stringent as evidenced by the binding affinity of AII(3-7) (K(D) = 20.9+/-2.1 nM). Neither AII, AIII, Sar1,Ile8-AII, Dup 753 nor CGP42112A appear to bind, indicating that this binding site is neither the AT1 nor AT2 sites described for AII/AIII. Autoradiographic analysis of hippocampus binding confirms the inability of Sar1,Ile8-All to compete for [I-125]AII(3-8) binding. Conversely AII(3-8) was unable to displace [I-125]Sar1,Ile8-AII binding.