Cellular and subcellular distribution of exogenously administered renal renin in rat liver and kidney

Using highly purified 125I-labeled rat renal renin, we have demonstrated that both the liver and kidney are responsible for clearance of renal renin. In the present study, light and electron microscope autoradiography of intravenously administered 125I-labeled rat renal renin was performed in rat liver and kidney to observe the cellular and subcellular distribution of the renin. Fifteen and 60 min after the injection, the liver and kidneys were removed and fixed with 0.1 M sodium phosphate buffer, pH 6.8, containing 2.5% glutaraldehyde and 0.5% tannic acid, which allowed for the removal of breakdown products of the labeled renin, and then autoradiography was performed. In the liver, silver grains were mainly localized in Kupffer cells and not in hepatocytes. In the kidney, silver grains were evident in the proximal tubule cells. In both liver and kidney cells, silver grains were mainly located over the lysosomes. Gel permeation high-performance liquid chromatography analysis of the liver and kidney extracts indicated two main fractions, including immunoreactive 125I-renin and the breakdown products (free 125I and 125I-tyrosine). In conclusion, circulating renal renin is mainly taken up by Kupffer cells and proximal tubule cells and is subsequently transported to the lysosomes to be degraded. These results, taken together with our previous finding that nonglycosylated submaxillary renin does not distribute in the liver, suggest that the carbohydrate moieties of renal renin are necessary for the recognition by Kupffer cells.