Stimulation of the glucuronic acid pathway in isolated rat liver cells by phenobarbital

Abstract

1. 1. Administration of phenobarbital to suspensions of isolated rat hepatocytes resulted within 90 min in an enhanced synthesis of d-glucaric acid, l-ascorbic acid and uridine diphosphate glucuronic acid (UDPGA). 2. 2. No alterations in the in vitro activities of UDPGdehydrogenase and UDPglucuronyltransferase were found within 120 min after treatment of the cells with phenobarbital. 3. 3. At increasing phenobarbital concentrations the uridine diphosphate glucose (UDPG) level increased significantly whereas a decrease in the glycogen concentration occurred. 4. 4. C 14-labeling experiments showed a lower rate of d-glucose-1-C 14 incorporation in glycogen (expressed as per mg protein) of phenobarbital treated cells, whereas an equal increase in specific activities as a function of time was observed in both phenobarbital treated and control cells. This strongly suggests that the lowered glycogen concentration, after treatment with phenobarbital, is caused by a decreased synthesis of glycogen, resulting in an enhanced availability of UDPG. On account of these results it has been concluded that a stimulation of the D-glucuronic acid pathway most probably is based on an inhibition of glycogen synthesis.