Increased hepatic phosphoprotein phosphatase activity induced by phenobarbital and its supression by cycloheximide and SKF 525-A

Abstract Phenobarbital influences the activity of liver phosphoprotein phosphatase in rats. Daily doses of 100 mg/kg body weight induced a significant increase in phosphoprotein phosphatase activity after the fourth injection, with a plateau after the fifth dose. The rate of induction and the magnitude of response were found to be dependent on the daily doses of phenobarbital. The marked sensitivity of the enzyme induction to cycloheximide suggests that the formation of new enzyme protein is involved in the process. SKF 525-A administered 40 min before phenobarbital, completely suppressed the induced increase of phosphoprotein phosphatase. An additional series of phenobarbital injection to pretreated rats, after a pause of 5 days, when regression of drugmetabolizing enzymes and of phosphoprotein phosphatase have been reached, provoked an even more pronounced increase in the enzyme activity than the original treatment. The possible relationship between the activity of phosphoprotein phosphatase and the activity of drug-metabolizing enzymes has been investigated.