PHENOBARBITAL INDUCTION OF ALPHA(1)-ACID GLYCOPROTEIN IN PRIMARY RAT HEPATOCYTE CULTURES

The serum level of rat alpha(1)-acid glycoprotein is significantly increased by treatment with phenobarbital, and in vice studies have shown that phenobarbital seems to act mainly at the transcriptional level. To show the direct mediating effect of phenobarbital on alpha(1)-acid glycoprotein gene expression, we investigated the ability of primary cultured rat hepatocytes to respond to in vitro phenobarbital administration. Phenobarbital increased both alpha(1)-acid glycoprotein secretion and corresponding mRNA levels in primary rat hepatocytes cultured on matrigel. Used in combination with interleukin-1, interleukin-6 and dexamethasone, phenobarbital had an additive or synergistic effect on alpha(1)-acid glycoprotein synthesis. These results show that (a) phenobarbital acts directly on hepatocytes by increasing alpha(1)-acid glycoprotein gene expression and (b) this effect is mediated by a specific mechanism independent of pathways involved in alpha(1)-acid glycoprotein induction by interleukin-1, interleukin-6 and glucocorticoids.