EFFECT OF PHENOBARBITAL ON HEPATIC GAP JUNCTIONAL INTERCELLULAR COMMUNICATION IN RATS

The effects of in vivo exposure to phenobarbital (PB) on hepatic gap j unctional intercellular communication (GJIC) and connexin protein expr ession in Sprague-Dawley rats were examined by in vivolin vitro dye-tr ansfer assay, immunohistochemical staining, and by Western blot analys is. PB (50 mg/kg) was administered orally once a day for up to 6 wk. T he average size of the dye spread after injection of Lucifer Yellow de creased at week 1 and remained at the same level until week 6. The are a 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 an d number of connexin 26 (Cx26) spots per hepatocytes showed no clear c hange through the experimental periods. The decreased level of Cx32 pr otein 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 local ization may be responsible for this effect.