Clearance and metabolism of glandular kallikrein in the rat. 1985

S F Rabito, and M Seto, and S R Maitra, and O A Carretero

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)

UI MeSH Term Description Entries
D007457 Iodine Radioisotopes Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes. Radioisotopes, Iodine
D007610 Kallikreins Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increase vascular permeability and affect smooth muscle. They act as infertility agents in men. Three forms are recognized, PLASMA KALLIKREIN (EC 3.4.21.34), TISSUE KALLIKREIN (EC 3.4.21.35), and PROSTATE-SPECIFIC ANTIGEN (EC 3.4.21.77). Kallikrein,Kininogenase,Callicrein,Dilminal,Kallidinogenase,Kalliginogenase,Kallikrein A,Kallikrein B',Kallikrein Light Chain,Kinin-Forming Enzyme,Padutin,alpha-Kallikrein,beta-Kallikrein,beta-Kallikrein B,Enzyme, Kinin-Forming,Kinin Forming Enzyme,Light Chain, Kallikrein,alpha Kallikrein,beta Kallikrein,beta Kallikrein B
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D009392 Nephrectomy Excision of kidney. Heminephrectomy,Heminephrectomies,Nephrectomies
D010664 Phenylmethylsulfonyl Fluoride An enzyme inhibitor that inactivates IRC-50 arvin, subtilisin, and the fatty acid synthetase complex. Benzenemethanesulfonyl Fluoride,Phenylmethanesulfonyl Fluoride,Fluoride, Benzenemethanesulfonyl,Fluoride, Phenylmethanesulfonyl,Fluoride, Phenylmethylsulfonyl
D011480 Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat

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