Hepatic processing of recombinant human renin: Mechanisms of uptake and degradation

D. L. Marks, L. J. Kost, S. M. Kuntz, J. C. Romero, N. F. LaRusso

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Biologically active 125I-Bolton-Hunter-labeled recombinant human renin (BH-renin) was used to study hepatic processing of renin both in vivo in bile fistula rats and in vitro in isolated perfused rat livers. BH-renin was composed mainly (80%) of a form that bound to concanavalin A-agarose (CB-renin). Twenty minutes after femoral venous injection of CB-renin in vivo, 47% of injected radiolabel was present in liver. Hepatic uptake of CB-renin was inhibited in a dose-dependent manner by mannosylated bovine serum albumin (MBSA) and mannan, but was unaffected by asialofetuin and mannose 6-phosphate. MBSA also significantly inhibited the plasma disappearance of endogenous renin in kidney-ligated rats. Cell separation techniques and light microscopic autoradiography showed that CB-renin was preferentially cleared by hepatic nonparenchymal cells via the mannose receptor, but was also cleared by hepatocytes via an unidentified mechanism. Tissue fractionation demonstrated that after injection of CB-renin, radiolabel was concentrated in lysosome-enriched liver fractions. In the liver, CB-renin was rapidly degraded to trichloroacetic acid-soluble fragments, which accumulated in urine and bile. Leupeptin, an inhibitor of lysosomal proteases, decreased degradation of CB-renin by 60%; vinblastine and colchicine, microtubule binding agents, each inhibited CB-renin degradation by 40%. Our results show that the liver plays a major role in the regulation of plasma renin levels via clearance by the mannose receptor on nonparenchymal cells and subsequent degradation in lysosomes.

Original languageEnglish (US)
Pages (from-to)G349-G358
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number2 24-2
StatePublished - 1991


  • Endothelial cells
  • Liver
  • Lysosomes
  • Mannose receptor
  • Plasma clearance

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


Dive into the research topics of 'Hepatic processing of recombinant human renin: Mechanisms of uptake and degradation'. Together they form a unique fingerprint.

Cite this