Kinetics of in vivo inhibition of tissue cathepsin D by pepstatin A.
1. We have investigated the kinetics of inhibition of cathepsin D in heart, liver and skeletal muscle of CD-1 mice following administration of 25, 50, 100 and 200 mg/kg i.p. of pepstatin A, a specific inhibitor of this protease. 2. In the liver, a significant inhibition of cathepsin D occurred up to at least 15 days, whereas, in heart and skeletal muscle, this inhibition lasted for a much shorter period of time. 3. These results show that the recovery of enzyme activity to normal values is dose-dependent and that, at the same dose level, marked differences occur in the recovery of enzyme activity in these organ tissues, the liver being the most sensitive one.
Leto
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Istituto di Farmacologia, Policlinico P. Giaccone, Palermo, Italy.
Tumminello
F M
FM
Gebbia
N
N
Rausa
L
L
D000818:Animals; D002402:Cathepsin D / Q000037:antagonists & inhibitors*; D005260:Female; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D051379:Mice; D009132:Muscles / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D009842:Oligopeptides / Q000494:pharmacology*; D010436:Pepstatins / Q000494:pharmacology*
D009842:Oligopeptides; D010436:Pepstatins; C014195:Streptomyces pepsin inhibitor; D002402:Cathepsin D; C031375:pepstatin