Characterization of angiotensin binding to gerbil brain membranes using [125I]angiotensin III as the radioligand

The observation that an Angiotensin II (AII)-sensitive species, the gerbil, exhibited little or no [125I]AII binding to brain membranes led to the hypothesis that AII's central action may be mediated by smaller and/or modified fragments of AII. This possibility was assessed, in part, by examining the ability of gerbil brain membranes to specifically bind [125I]desAsp1 AII (AIII), a heptapeptide fragment of AII. Specific binding was evident throughout the gerbil brain with highest binding in the septum (containing the subfornical organ), anterior ventral third ventricular region, hypothalamus (containing the median eminence), and striatum. This binding was found to possess many of the properties commonly associated with binding to membrane bound receptors. The binding within the circumventricular organs had characteristics that set them apart from the other central nervous tissues examined. Both the olfactory bulb and adrenal gland appeared to have two different angiotensin binding sites. It appears that the binding sites within the brain interact with a product of the metabolism of AIII or AII rather than the peptides themselves. The results suggest that [125I]AIII appears to be a better ligand than [125I]AII in the binding assay because it is more readily degraded to another substance.