CENTRAL ANGIOTENSIN-IV BINDING-SITES - DISTRIBUTION AND SPECIFICITY IN GUINEA-PIG BRAIN

Our laboratory has reported previously that a unique binding site spec ific for the hexapeptide angiotensin (A)II(3-8), now referred to as AI V, is present in a number of tissues including bovine adrenal gland, r abbit and guinea pig heart and guinea pig kidney, liver, lung, uterus and brain. The present results extend previous findings in the guinea pig brain and identity binding sites for AIV in the neocortex, paleoco rtex, hippocampus, medial habenula, superior and inferior colliculi, c audate putamen, thalamus, dorsal tegmentum, central gray, red nucleus, inferior olivary, oculomotor and hypoglossal nuclei and cerebellum. B inding of [I-125]AIV in selected regions was shown to be of high affin ity (K(d) = 0.60-1.47 nM), saturable (maximal number of binding sites = 181-449 fmol/mg of protein) and specific. This binding site was show n to be distinct from the AT1 and AT2 sites with K(i) values > 10(-4) M for DuP 753, CGP42112A and PD123177. Changes at the N-terminal of th e peptide, either by removal of the valine or by extension of the pept ide, resulted in a large decrease in binding affinity. In contrast, C- terminal extensions resulted in little change in affinity for the bind ing site. Guanosine 5'-0-(3-thiotriphosphate) was shown to have no eff ect on binding, suggesting that the guinea pig brain binding site is n ot G-protein-linked. Potential functions associated with this newly di scovered A binding site are discussed.