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Anticoagulant action of vanadate
T Funakoshi1, H Shimada, S Kojima
1Department of Hygenic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Chemical & Pharmaceutical Bulletin
|January 1, 1992
Summary
Sodium orthovanadate (vanadate) prolongs blood clotting time by inhibiting thrombin and factor Xa activity. Amiloride counteracts this effect, suggesting a protective role in vanadate-induced coagulation changes.
Area of Science:
- Biochemistry
- Hematology
Background:
- Sodium orthovanadate (vanadate) is known to affect various enzymatic activities.
- Its precise impact on the coagulation cascade requires further elucidation.
Purpose of the Study:
- To investigate the effect of vanadate on human plasma clotting time.
- To determine the mechanisms underlying vanadate's influence on coagulation factors.
Main Methods:
- Assessing plasma clotting time with varying vanadate concentrations.
- Evaluating the amidolytic activity of coagulation factors (thrombin, factor Xa) and other proteases (trypsin, alpha-chymotrypsin) in the presence of vanadate and amiloride.
Main Results:
- Vanadate dose-dependently prolonged plasma clotting time.
- This prolongation was antagonized by amiloride and additive to heparin's effect.
- Vanadate inhibited the amidolytic activity of thrombin, factor Xa, and trypsin, but not alpha-chymotrypsin.
- Amiloride protected factor Xa and thrombin from vanadate-induced inhibition.
Conclusions:
- Vanadate prolongs plasma clotting time primarily by inhibiting the enzymatic activity of key coagulation factors like thrombin and factor Xa.
- Vanadate exhibits a preference for inhibiting trypsin-like serine proteases.
- Amiloride demonstrates a protective effect against vanadate's inhibitory action on coagulation enzymes.