Clearance and metabolism of glandular kallikrein in the rat
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. The authors injected either active /sup 125/I-kallikrein or kallikrein inactivated with phenylmethylsulfonyl fluoride (/sup 125/I-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 /sup 125/I-kallikrein. Removal of the kidneys did not significantly affect the clearance of active kallikrein. On the other hand, inactive /sup 125/I-PMSF-kallikrein was removed from blood faster than active /sup 125/I-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 /sup 125/I-PMSF-kallikrein was markedly prolonged by bilateral nephrectomy. Active /sup 125/I-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. The authors 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.
- OSTI ID:
- 5043398
- Journal Information:
- Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States)
- Country of Publication:
- United States
- Language:
- English
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VASODILATORS
BLOOD-PLASMA CLEARANCE
METABOLISM
RENAL CLEARANCE
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
ENZYME INHIBITORS
IODINE 125
KIDNEYS
LABELLED COMPOUNDS
LIVER
NEPHRECTOMY
PEPTIDE HYDROLASES
RATS
SPLEEN
TISSUE DISTRIBUTION
TRACER TECHNIQUES
URINE
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
CARDIOVASCULAR AGENTS
CLEARANCE
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
EXCRETION
GLANDS
HYDROLASES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MATERIALS
MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ORGANS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SURGERY
VERTEBRATES
WASTES
550501* - Metabolism- Tracer Techniques