Amiloride selectively inhibits the urokinase‐type plasminogen activator

作者：Jean‐Dominique Vassalli, Dominique Belin · 发表于：FEBS Letters · 年份：1987 · DOI：10.1016/0014-5793(87)80039-x · 被引用次数：386 · 研究领域：Protease and Inhibitor Mechanisms、Blood Coagulation and Thrombosis Mechanisms、Peptidase Inhibition and Analysis

The diuretic drug amiloride, an inhibitor of Na+ uptake, competitively inhibits the catalytic activity of the urokinase-type plasminogen activator (u-PA), with a Ki of 7 X 10(-6) M. Generation of plasmin, cleavage of peptide substrates, and interaction of u-PA with a specific macromolecular proteinase inhibitor are all prevented in the presence of the drug. In contrast, amiloride does not affect the activity of either tissue-type plasminogen activator, plasmin, plasma kallikrein or thrombin. The inhibition of u-PA by amiloride may be related to the previously reported inhibition of u-PA-type enzymes by Na+. Amiloride or related compounds could prove useful in selectively controlling u-PA-catalyzed extracellular proteolysis.