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Inhibition of the thrombin-platelet reactions by DuP 714.

Abstract：

:The efficacy and specificity of a novel synthetic thrombin inhibitor, DuP 714, on thrombin-induced elevation of cytoplasmic calcium, fibrinogen binding and aggregation in human platelets were examined. Thrombin (0.5 U/ml) stimulated an increase in [125I]fibrinogen binding in gel-filtered platelets which was blocked by DuP 714 with an IC50 value of 2 nM. Thrombin (1 U/ml)-induced elevation of intracellular [Ca2+]i was also blocked by DuP 714 with an IC50 value of 67 nM. A much higher concentration of thrombin (25 U/ml) was used to stimulate aggregation with heparinized platelet-rich plasma. Under these conditions, micromolar concentrations of DuP 714 were needed to inhibit thrombin. In all of these preparations, DuP 714 at concentrations as high as 10(-5) M had no intrinsic effects and did not affect the responses induced by arachidonate, ADP, collagen, epinephrine, vasopressin and serotonin. These data indicate that DuP 714 is a potent and specific thrombin inhibitor capable of arresting the actions of thrombin on human fibrin formation and platelet aggregation and secretion. It may serve as a potential antithrombotic agent for various forms of thrombotic disorders.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Chiu AT,Mousa SA,Pease LJ,Roscoe WA,Bozarth JM,Reilly TM,Smith RD,Timmermans PB

doi

10.1016/0006-291x(91)91742-u

subject

Has Abstract

pub_date

1991-09-30 00:00:00

pages

1500-8

issue

3

eissn

0006-291X

issn

1090-2104

pii

0006-291X(91)91742-U

journal_volume

179

pub_type

杂志文章

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