Effect of phenobarbital on hepatic gap junctional intercellular communication in rats

The effects of in vivo exposure to phenobarbital (PB) on hepatic gap junctional intercellular communication (GJIC) and connexin protein expression in Sprague-Dawley rats were examined by in vivolin vitro dye-transfer assay, immunohistochemical staining, and by Western blot analysis. PB (50 mg/kg) was administered orally once a day for up to 6 wk. The average size of the dye spread after injection of Lucifer Yellow decreased at week 1 and remained at the same level until week 6. The area and number of connexin 32 (Cx32) spots per hepatocyte in the central zone of liver lobules decreased from week 1 to week 6, but no change of Cx32 spots in the peripheral zone was observed. The average area and number of connexin 26 (Cx26) spots per hepatocytes showed no clear change through the experimental periods. The decreased level of Cx32 protein in plasma membranes was observed in the PB group. These results suggest that PB, a liver tumor-promoting agent, inhibits hepatic GJIC in vivo in rats and that aberrant Cx32 protein expression and/or localization may be responsible for this effect.