AJP - Endocrinology and Metabolism, Vol 253, Issue 6 E621-E628, Copyright © 1987 by American Physiological Society
Cellular and subcellular distribution of exogenously administered renal renin in rat liver and kidney
S. Kim, H. Iwao, N. Nakamura, F. Ikemoto, K. Yamamoto, V. Mizuhira and J. Yokofujita
Department of Pharmacology, Osaka City University Medical School, Japan.
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.
