Angiotensin II in the central nervous system in the rat

Abstract

Characteristics and functional activity of Angiotensin II (AII) neuronal receptors were studied using binding and intracellular recording methods. Characteristics of AII binding allowed definition of two distinct classes of high and low affinity binding sites. The effects of AII on the electrophysiological membrane properties of neurones were investigated using cultured mouse spinal cord (SC). AII induced changes in membrane potential and input resistance which varied according to the applied concentration of peptide. These data agreed with binding results suggesting two classes of AII neuronal receptors. Although angiotensin II-like material is found in the rat brain by RIA and immunochemistry, the presence of authentic angiotensin II (AII) is a point for discussion. Using RIA and radio-receptor assay (RRA), we found AII like peptides. However, chromatographic separation by gel filtration has revealed that this material is not authentic AII but consists of compounds of higher molecular weight. The recognition of the same material, both by AII antibodies (RIA) and AII binding sites (RRA) suggests that precursors containing AII sequences exist in the rat brain. We incubated rat brain with 3H-angiotensin I (AI) at 37 degrees C and analysed the resulting 3H-peptides (HPLC). Authentic 3H-AII was not detected, but two smaller peptides appeared (peak alpha et beta). The same peaks appeared when rat brain was incubated with 3H-AII. We have only been able to reveal 3H-AII formation from 3H-AI by inhibiting AII angiotensinases with excess of AII or low temperature (22 degrees C or 12 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)