In vivo behavior of detergent-solubilized purified rabbit thrombomodulin on intravenous injection into rabbits

Journal Article · Thu Feb 01 04:00:00 EST 1990 · Journal of Laboratory and Clinical Medicine; (USA)

OSTI ID:7027432

Ehrlich, H J; Esmon, N L; Bang, N U ^[1]

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1. Eli Lilly and Company, Indianapolis, IN (USA)

Thrombomodulin is a thrombin endothelial cell membrane receptor. The thrombomodulin-thrombin complex rapidly activates protein C resulting in anticoagulant activity. We investigated the anticoagulant effects and pharmacokinetic behavior of detergent-solubilized purified rabbit thrombomodulin labeled with iodine 125 when intravenously injected into rabbits. Thrombomodulin half-life (t1/2) was determined by tracking the 125I-radiolabeled protein and the biologic activity as determined by the prolongation of the activated partial thromboplastin time (APTT) and thrombin clotting time (TCT). When 200 micrograms/kg 125I-thrombomodulin was injected into rabbits, the APTT and TCT were immediately prolonged, whereas no effect on the prothrombin time was seen. In vitro calibration curves enabled us to convert the prolongations of the clotting times into micrograms per milliliter thrombomodulin equivalents. The best fit (r greater than 0.99) for the disappearance curves was provided by a two-compartment model with mean t1/2 alpha (distribution phase) of 18 minutes for 125I, 12 minutes for APTT, and 20 minutes for TCT, and mean t1/2 beta (elimination phase) of 385 minutes for 125I, 460 for APTT, and 179 for TCT. The administration of two doses of endotoxin (50 micrograms/kg) 24 hours apart did not accelerate the turnover rate of 125I-thrombomodulin as measured by the disappearance of 125I from the circulation. Thus, detergent-solubilized purified thrombomodulin administered intravenously circulates in a biologically active form for appreciable time periods.

• OSTI ID: 7027432
• Journal Information: Journal of Laboratory and Clinical Medicine; (USA), Journal Name: Journal of Laboratory and Clinical Medicine; (USA) Vol. 115:2; ISSN JLCMA; ISSN 0022-2143
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BLOOD COAGULATION
BODY
COAGULANTS
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENDOTHELIUM
ENZYMES
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROLASES
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
INTRAVENOUS INJECTION
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PEPTIDES
PROTEINS
RABBITS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
SERINE PROTEINASES
SOLUBILITY
THROMBIN
TISSUES
TRACER TECHNIQUES
VERTEBRATES