Characteristics of angiotensin II binding sites in the neostriatum of the rat brain.
Angiotensin II binding activity of striatal cell membranes of the rat was examined using [(125)I]angiotensin II. The characteristics of displacement of bound [(125)I]angiotensin II by unlabelled Ileu(5)-angiotensin II allowed definition of two pharmacologically distinct classes of binding sites: one recognized by low concentrations of angiotensin II (IC(50) = 0.28 nM) and a second composed of sites poorly recognized by angiotensin II(IC(50) = 0.45 ?M). Scatchard analysis of the saturation curve with increasing [(125)I]angiotensin II allowed determination of characteristics of the angiotensin II high affinity binding site: K(4) = 0.36 nM, B(max) = 83.9 fmol/g original tissue weight. Among angiotensin II related peptides tested, Sar(1)-Ileu(8)-angiotensin II was the most potent in displacing bound [(125)I]angiotensin II. Neostriatal lesions with kainic acid suggest that this class of angiotensin II high affinity binding sites were primarily located on intrinsic neurones, since the drop in angiotensin II binding (?46%) was associated to the reduction occurring in the activity of choline acetyltransferase (?50.3%). These findings support the idea that functional angiotensin II receptors exist on membranes of intrinsic neurones in the rat neostriatum as previously indicated by microiontophoretic application experiments.
Simonnet
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I.N.S.E.R.M. U176-Unité de Recherches de Neurobiologie des Comportements, Domaine de Carreire, Rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
Vincent
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JD