Rapid neural regulation of muscle urokinase-like plasminogen activator as defined by nerve crush

Abstract

Muscle plasminogen activators (PAs), such as urokinase-like PA and, to a lesser extent, tissue PA, increase dramatically after denervation induced by axotomy. The PA/plasmin system has also been implicated in degradation of specific components of the muscle fiber basement membrane after local activation of plasminogen. These results suggest that neural regulation of muscle extracellular matrix metabolism accompanies or precedes regeneration after injury and is mediated by activation of PAs. In the present study, we have used nerve crush to explore the neural regulation of muscle PA activities directly after subtotal axon interruption and during the process of reinnervation. Muscle contraction after nerve stimulation and estimation of choline acetyltransferase activity were used to monitor reinnervation. Within 24 hr of nerve crush, muscle urokinase (but not tissue PA) activity rose in soluble and membrane-bound muscle fractions, as shown by an amidolytic assay and a fibrin zymography. Membrane-bound activity was 5-fold higher than cytosol activity, but there was no shift between cellular compartments during the time course of denervation. Coincident with the return of choline acetyltransferase activity and muscle contractility, muscle urokinase returned almost to baseline levels. These results show tight regulation of muscle urokinase levels by some neural influence.