Conversion to renin of exogenously administered recombinant human prorenin in liver and kidney of monkeys

Abstract

Highly purified recombinant human prorenin, labeled with 125I (125I-prorenin), was intravenously given to monkeys to examine the possible in vivo conversion of this prorenin to renin. 125I-prorenin and 125I-renin were detected using specific anti-prorenin prosegment antibody and anti-renin antibody, respectively. The plasma disappearance of immunoreactive 125I-prorenin in marmosets showed two exponential components with a half-life of 10.4 +/- 0.2 min for the rapid component and 165.7 +/- 12.6 min for the slow component. Fifteen minutes after the injection of 125I-prorenin, 38.7 +/- 2.8 and 3.9 +/- 0.5% of the administered dose accumulated in the liver and kidney, respectively. Less than 1% of the dose injected distributed in the other organs, including the brain, submandibular gland, lung, heart, aorta, adrenal gland, spleen, uterus, ovary, and testis. Thus the labeled prorenin was predominantly taken up by the liver and kidney. Analysis of liver and kidney extracts and plasma, by both gel permeation high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, demonstrated that 125I-prorenin (Mr = 46,000) taken up by the liver and kidney was significantly converted to 125I-renin (Mr = 42,000), whereas only a negligible amount of 125I-renin (Mr = 42,000) was present in the plasma. Although there seems to be no activation of prorenin in the blood circulation, prorenin does seem to be activated by the liver and kidney.