Influence of Cl- on organic anion transport in short-term cultured rat hepatocytes and isolated perfused rat liver.
Transport of 35S-labeled sulfobromophthalein [35S]BSP was studied in short-term cultured rat hepatocytes incubated in bovine serum albumin. At 37 degrees C, initial uptake of [35S]BSP was 5-10-fold that at 4 degrees C, linear for at least 15 min, saturable, inhibited by bilirubin, and reduced by greater than 70% after ATP depletion or isosmotic substitution of sucrose for NaCl in medium. Replacement of Na+ by K+ or Li+ did not alter uptake, whereas replacement of Cl- by HCO-3 or gluconate- reduced uptake by approximately 40%. Substitution of Cl- by the more permeant NO-3 enhanced initial BSP uptake by 30%. Efflux of [35S]BSP 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 [3H]bilirubin 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.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001663:Bilirubin / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism / Q000494:pharmacology*; D008094:Lithium / Q000378:metabolism; D018021:Lithium Chloride; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010477:Perfusion; D011189:Potassium Chloride / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000378:metabolism; D013448:Sulfobromophthalein / Q000378:metabolism
D002712:Chlorides; D013448:Sulfobromophthalein; D012965:Sodium Chloride; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D008094:Lithium; D018021:Lithium Chloride; D001663:Bilirubin