Clearance and metabolism of glandular kallikrein in the rat

Abstract

This study was undertaken to characterize the clearance of circulating rat glandular kallikrein and to determine the contribution of various organs and the urinary excretion to the removal of glandular kallikrein from the bloodstream. We injected either active 125I-kallikrein or kallikrein inactivated with phenylmethylsulfonyl fluoride (125I-PMSF-kallikrein) intravenously into intact or nephrectomized rats and then studied the disappearance rate of trichloroacetic acid (TCA)-precipitable radioactivity from the circulation. Inactivation by PMSF markedly reduced the binding of kallikrein to plasma protease inhibitors. The removal rate of the acid-precipitable radioactivity fit a biexponential curve for both active and inactive kallikrein. In the intact rats approximately 50% of the radioactivity was removed from the circulation 30 min after the injection of active 125I-kallikrein. Removal of the kidneys did not significantly affect the clearance of active kallikrein. On the other hand, inactive 125I-PMSF-kallikrein was removed from blood faster than active 125I-kallikrein in normal animals. Approximately 50% of the radioactivity was removed from the circulation 8 min after the injection, and the half-life of inactive 125I-PMSF-kallikrein was markedly prolonged by bilateral nephrectomy. Active 125I-kallikrein was taken up by tissues, particularly the liver and the kidney. In urine, less than 2% of the radioactivity was excreted in 60 min as TCA-precipitable material. We concluded that glandular kallikrein is cleared rapidly from the circulation of the rat, probably in the form of a complex with a plasma protease inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)