The effect of phenobarbital on the transcriptional activity of liver.

The effect of phenobarbital on the transcriptional activity of liver was studied by measuring the synthesis of RNA by suspensions of hepatocytes isolated from rats treated with phenobarbital for various time periods. The absolute rates of RNA synthesis by isolated hepatocytes were determined by measuring the incorporation of [3H]orotic acid into RNA as UMP and the specific radioactivity of the UTP pool. The specific radioactivity of the UTP extracted from hepatocytes isolated from phenobarbital-treated rats was consistently lower than that of the UTP pool of hepatocytes from untreated rats. Phenobarbital treatment increased the rate of RNA synthesis 10-fold over that observed for hepatocytes from untreated rats. The maximum rate of RNA synthesis was observed 16-18 h after phenobarbital administration. Phenobarbital treatment also affected the nuclear-cytoplasmic transport of RNA by isolated hepatocytes. Immediately after phenobarbital treatment, the transport of RNA decreased; however, 24 h after phenobarbital administration, the transport of RNA was increased 4-fold. An increase in the synthesis of RNA in vivo by liver was found 18 h after phenobarbital treatment, and the incubation of suspensions of hepatocytes with various concentrations of phenobarbital increased RNA synthesis significantly.