Paradoxical effect of leupeptin in vivo on cathepsin B activity

Leupeptin is a potent inhibitor of cathepsin B in vitro and is presumed to act in a similar manner in vivo. It is currently being used in several laboratories to examine the role of lysosomal proteinases such as cathepsin B in mouse models of muscular dystrophy. This report clearly demonstrates that leupeptin in adequate concentrations in vivo, is a potent stimulator of cathepsin B activity in striated muscle, heart, liver and kidney of the mouse. This paradoxical effect indicates that care is required in the interpretation of the results of the use of leupeptin as a cathepsin B inhibitor in vivo and that its use as an antiprotease for therapeutic purposes may be limited. Studies on CBZ-Phe-Ala-CHN2 demonstrated that this agent, when administered in vivo, inhibited Cathepsin B in the tissues assayed.