Turnover of 125I-labelled tissue kallikrein following intraduodenal or intravenous administration
(2001) In Scandinavian Journal of Clinical and Laboratory Investigation 61(1). p.57-67- Abstract
UNLABELLED: Tissue kallikrein is released in the body both physiologically and in many inflammatory disorders. Little is, however, known about the turnover of released tissue kallikrein in humans. Approximately 1 mg of tissue kallikrein (mol wt 43,000 Da) was purified from 85 L human urine by: (1) ultracentrifugation, (2) filtration through an aprotinin-coupled Sepharose 4B column, followed by (3) gel filtration over a Sephadex G-75 column. The elimination, after intraduodenal or intravenous administration of purified tissue kallikrein radiolabelled with 125I, was followed by collecting serial samples of plasma, urine and faeces from three volunteers. Within 72 h, about 96% of the intraduodenally administered radioactivity had been... (More)
UNLABELLED: Tissue kallikrein is released in the body both physiologically and in many inflammatory disorders. Little is, however, known about the turnover of released tissue kallikrein in humans. Approximately 1 mg of tissue kallikrein (mol wt 43,000 Da) was purified from 85 L human urine by: (1) ultracentrifugation, (2) filtration through an aprotinin-coupled Sepharose 4B column, followed by (3) gel filtration over a Sephadex G-75 column. The elimination, after intraduodenal or intravenous administration of purified tissue kallikrein radiolabelled with 125I, was followed by collecting serial samples of plasma, urine and faeces from three volunteers. Within 72 h, about 96% of the intraduodenally administered radioactivity had been excreted in urine, and approximately 5.4% in faeces, mainly as 125I. No intact 125I-tissue kallikrein was found in plasma, urine or faeces after the intraduodenal instillation of the protein. The plasma half-life of 125I-tissue kallikrein up to 3 h after intravenous injection was 9 min and, thereafter, 20 h. The 125I-tissue kallikrein was quickly bound to a plasma protein with a mol wt of about 67 kDa, but some of the radioiodinated tissue kallikrein was still unbound 15 min after injection, judged by gel filtration on Sephadex G-200 columns. Most of the radioactivity was excreted in the urine as 125I, but about 4-6% was recovered as free 125I-tissue kallikrein.
CONCLUSION: The use of tissue kallikrein as an oral drug appears, therefore, to be useless. Tissue kallikrein released into plasma seems to be quickly bound to a protein with a mol wt of 67 kDa, probably kallistatin or Protein C inhibitor, but some tissue kallikrein seems to be unbound and may have some physiological or pathophysiological action. The unbound tissue kallikrein is, at least partly, cleared from the circulation by the kidneys, and tissue kallikrein in the urine may partly be derived from plasma.
(Less)
- author
- Bläckberg, M LU and Ohlsson, K
- organization
- publishing date
- 2001-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adult, Body Fluids/metabolism, Chromatography, Gel, Duodenum/metabolism, Feces/chemistry, Gastric Juice/metabolism, Humans, Injections, Intravenous, Iodine Radioisotopes, Isotope Labeling, Kallikreins/administration & dosage, Kinetics, Male
- in
- Scandinavian Journal of Clinical and Laboratory Investigation
- volume
- 61
- issue
- 1
- pages
- 11 pages
- publisher
- Informa Healthcare
- external identifiers
-
- scopus:0034745045
- pmid:11300612
- ISSN
- 0036-5513
- DOI
- 10.1080/00365510151068009
- language
- English
- LU publication?
- yes
- id
- 7425b2a1-bafe-42ae-b450-b42fffe684f4
- date added to LUP
- 2020-04-16 14:12:36
- date last changed
- 2024-01-02 09:05:47
@article{7425b2a1-bafe-42ae-b450-b42fffe684f4,
abstract = {{<p>UNLABELLED: Tissue kallikrein is released in the body both physiologically and in many inflammatory disorders. Little is, however, known about the turnover of released tissue kallikrein in humans. Approximately 1 mg of tissue kallikrein (mol wt 43,000 Da) was purified from 85 L human urine by: (1) ultracentrifugation, (2) filtration through an aprotinin-coupled Sepharose 4B column, followed by (3) gel filtration over a Sephadex G-75 column. The elimination, after intraduodenal or intravenous administration of purified tissue kallikrein radiolabelled with 125I, was followed by collecting serial samples of plasma, urine and faeces from three volunteers. Within 72 h, about 96% of the intraduodenally administered radioactivity had been excreted in urine, and approximately 5.4% in faeces, mainly as 125I. No intact 125I-tissue kallikrein was found in plasma, urine or faeces after the intraduodenal instillation of the protein. The plasma half-life of 125I-tissue kallikrein up to 3 h after intravenous injection was 9 min and, thereafter, 20 h. The 125I-tissue kallikrein was quickly bound to a plasma protein with a mol wt of about 67 kDa, but some of the radioiodinated tissue kallikrein was still unbound 15 min after injection, judged by gel filtration on Sephadex G-200 columns. Most of the radioactivity was excreted in the urine as 125I, but about 4-6% was recovered as free 125I-tissue kallikrein.</p><p>CONCLUSION: The use of tissue kallikrein as an oral drug appears, therefore, to be useless. Tissue kallikrein released into plasma seems to be quickly bound to a protein with a mol wt of 67 kDa, probably kallistatin or Protein C inhibitor, but some tissue kallikrein seems to be unbound and may have some physiological or pathophysiological action. The unbound tissue kallikrein is, at least partly, cleared from the circulation by the kidneys, and tissue kallikrein in the urine may partly be derived from plasma.</p>}},
author = {{Bläckberg, M and Ohlsson, K}},
issn = {{0036-5513}},
keywords = {{Adult; Body Fluids/metabolism; Chromatography, Gel; Duodenum/metabolism; Feces/chemistry; Gastric Juice/metabolism; Humans; Injections, Intravenous; Iodine Radioisotopes; Isotope Labeling; Kallikreins/administration & dosage; Kinetics; Male}},
language = {{eng}},
number = {{1}},
pages = {{57--67}},
publisher = {{Informa Healthcare}},
series = {{Scandinavian Journal of Clinical and Laboratory Investigation}},
title = {{Turnover of 125I-labelled tissue kallikrein following intraduodenal or intravenous administration}},
url = {{http://dx.doi.org/10.1080/00365510151068009}},
doi = {{10.1080/00365510151068009}},
volume = {{61}},
year = {{2001}},
}