Document Detail


The acceleration of the inhibition of platelet prothrombinase complex by heparin.
MedLine Citation:
PMID:  3954724     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The influence of heparin on the inhibition of factor Xa has been studied under conditions where factor Xa is bound to collagen-thrombin-stimulated platelets to form the prothrombinase complex. Unfractionated heparin was found to cause a concentration-dependent acceleration of the inhibition of the platelet prothrombinase complex up to a maximum rate constant of 4.1 X 10(7) M-1 X min-1 at heparin concentrations of 0.2 microM and above. This is equivalent to a 4800-fold acceleration over the rate constant for the inhibition in the absence of heparin, and is 6.8-fold lower than the rate constant for the inhibition of uncomplexed factor Xa in the presence of saturating concentrations of heparin which was determined as 2.8 X 10(8) M-1 X min-1. The effects of three Mr fractions of heparin were also studied. These were a gel-filtered heparin of Mr 15000, a gel-filtered heparin of Mr 6000 and a heparin oligosaccharide (primarily 8-10 monosaccharide units) prepared by nitrous acid depolymerization, each with high affinity for antithrombin III. These fractions all accelerated the rate of the antithrombin III inhibition of the platelet prothrombinase complex, with maximum rate constants of 6.8 X 10(7), 1.4 X 10(7) and 9.8 X 10(6) M-1 X min-1, respectively. On comparison with the effect of these heparin fractions on the rate of inhibition of uncomplexed factor Xa a progressively increasing disparity between the rate of inhibition of uncomplexed and complexed factor Xa was observed, rising from 1.7-fold with the oligosaccharide to 6.8-fold with the unfractionated heparin. A possible mechanism for this differential activity between uncomplexed and complexed factor Xa with the various heparin fractions is discussed in terms of an involvement of heparin binding to factor Xa.
Authors:
V Ellis; M F Scully; V V Kakkar
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  233     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1986 Jan 
Date Detail:
Created Date:  1986-04-16     Completed Date:  1986-04-16     Revised Date:  2010-09-13    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  161-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antithrombin III / metabolism
Blood Platelets / metabolism*
Factor V / antagonists & inhibitors*,  blood
Factor X / antagonists & inhibitors*,  blood,  metabolism
Factor Xa
Heparin / pharmacology*
Humans
Kinetics
Molecular Weight
Chemical
Reg. No./Substance:
0/prothrombinase complex; 9000-94-6/Antithrombin III; 9001-24-5/Factor V; 9001-29-0/Factor X; 9005-49-6/Heparin; EC 3.4.21.6/Factor Xa
Comments/Corrections

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