Influence of Cl- on Organic Anion Transport in Short-term Cultured Rat Hepatocytes and Isolated Perfused Rat Liver

Transport of 35S-labeled sulfobromophthalein V'SIBSP was studied in short-term cultured rat hepatocytes incubated in bovine serum albumin. At 37°C, initial uptake of V35SIBSP was 5-10fold that at 4°C, linear for at least 15 min. saturable, inhibited by bilirubin, and reduced by> 70 % after ATP depletion or isosmotic substitution of sucrose for NaCI in medium. Replacement of Na+ by K+ or Li ' did not alter uptake, whereas replacement of Cl- by HCO3 or gluconate- reduced uptake by-40%. Substitution of Cl- by the more permeant NO- enhanced initial BSP uptake by 30%. Efflux of V5SIBSP from cells to media was inhibited by 40 % after ATP depletion or sucrose substitution. To confirm these results in a more physiologic system, transport of 3Hlbilirubin was studied in isolated livers perfused with control medium or medium in which Cl- was replaced by gluconate-. Perfusion data analyzed by the model of Goresky, revealed 40-50 % reductions in influx and efflux with gluconate- substitution. These results are consistent with existence of a Cl-/organic anion-exchange mechanism similar to that described by others in renal tubules