Protease Inhibitors Reduce Effects of Denervation on Muscle End‐Plate Acetylcholinesterase

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Abstract
The effects of certain protease inhibitors on end-plate acetylcholinesterase (AChE) activity, and on wet wt and total protein, were studied in vivo in intact and denervated anterior gracilis muscles from the rat. A combination of leupeptin, pepstatin and aprotinin, administered intraarterially, partly prevented the early (24 h) denervation-induced decrease in muscle wt and protein content. Leupeptin and aprotinin, alone or in combination, markedly reduced the decay of AChE activity in the denervated muscles; only pepstatin was ineffective. Effects were additive, i.e., the inhibitors in combination were more effective than when used separately. None of the inhibitors, at the concentrations used, affected AChE activity directly. No significant effect was found during processing of the muscle samples. The initial decay of AChE activity with denervation was effectively reduced by the inhibitors, probably through inactivation of proteolytic enzymes which are usually increased in denervated muscle.