Amiloride selectively inhibits the urokinase‐type plasminogen activator

Abstract

The diuretic drug amiloride, an inhibitor of Na⁺ uptake, competitively inhibits the catalytic activity of the urokinase-type plasminogen activator (u-PA), with a K _i of 7 × 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.