Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin, kepone, and polybrominated biphenyls on transport systems in isolated rat hepatocytes.

Adult male rats recived intraperitoneal injections of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 10 μg/kg), polybrominated biphenyls (PBBs, 200 mg/kg), Kepone (5 mg/kg/day for 5 days), or vehicle, and isolated hepatocytes were prepared 10, 3, or 1 day after injection of TCDD, PBBs, or Kepone, respectively. All treatments significantly increased the hepatic microsomal content of cytochrome P-450. The initial velocity of uptake (V₀; measured within the first 2 min), steady-state concentration (SS, measured over 1 hr), and an indirect estimate of an efflux rate constant, k_cf, were determined for ouabain and procaine amide ethobromide (PAEB). TCDD decreased V₀ and SS of ouabain but had no effect on k_cf for ouabain or any parameter of PAEB transport. PBBs tended to increase k_cf and significantly decreased SS of ouabain. The k_cf for PAEB was significantly increased, but V₀ and SS were not changed in PBB-treated rats. Kepone had no effect on V₀ of either substrate but significantly decreased SS and increased k_cf for ouabain. These data demonstrate that the ouabain transport system is selectively inhibited by TCDD and that PBBs may nonspecifically increase the rate of efflux of actively transported substrates from cell to medium.