Liver angiotensin II receptors in the rat: binding properties and regulation by dietary Na+ and angiotensin II

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Abstract
Recent evidence suggests that angiotensin II (AII) acts on the liver via specific receptors. The aims of this study were to examine the general binding properties of these receptors in the rat and to determine the role of dietary Na+ and AII in the regulation of AII receptors. Binding of 125I-labelled Ile5-AII to liver membranes was saturable and behaved as a single class of sites with an affinity (Ka) of 2·9 l/nmol and a Hill coefficient of 0·99. Kinetic analysis of AII binding gave estimates for the rates of association and dissociation of 42 l/μmol per min and 1·5 × 10−2/min respectively. The binding of analogues exhibited the following order of potency: Val5-AII > Ile5-AII > AIII > Sar1-Ala8-AII > Sar1-Gly8-AII > AI > des-Asp-AI > C4−C8 pentapeptide > Phe1-Tyr8-AII > neurotensin > luteinizing hormone-releasing hormone. Binding was enhanced by Mg2+ and Ca2+ and inhibited by EDTA and the reducing agent dithiothreitol. Low dietary Na+ affected in a biphasic manner both the Ka and concentration (Ro) of liver AII receptors. Initially, Ro decreased from 25·9±3·8 (control) to 16±1·9 (s.e.m.) pmol/g tissue by 1·5 days but thereafter it rapidly increased to 47·3±8·7 pmol/g tissue (3·5 days) and remained elevated to the end of the experiment, 8·5 days later. The Ka initially increased from 2·7±0·3 (control) to 4·3±0·5 l/nmol (1·5 days) and then decreased steadily to 1·2±0·1 l/mol (8·5 days). The effect of AII was examined by infusing 24 pmol AII/kg per min for 5 days into the jugular vein by subcutaneous osmotic minipumps. The response was qualitatively similar to that for low dietary Na +. It was concluded that the rat liver has a high content of specific AII receptors that are responsive to changes in Na+ and AII. J. Endocr. (1985) 106, 103–111