Identification and characterization of a basolateral dicarboxylate/cholate antiport system in rat hepatocytes

摘要: The mechanisms and driving forces for the uptake of unconjugated bile acid cholate were investigated both in cultured rat hepatocytes liver basolateral (sinusoidal) plasma membrane (BLPM) vesicles. Determination initial rates [3H]cholate (0.1 microM) into confirmed that majority (75%) transmembrane transport was mediated by Na(+)-independent mechanisms. This portion consisted a pH-sensitive moiety representing nonionic diffusion, which may become quantitatively important at low pH high concentrations, as well saturable (Michaelis constant 7.4 microM), 4,4'-diisothiocyanostilbene-2,2'-disulfonic (DIDS)-sensitive moiety, suggesting involvement carrier. latter system functionally characterized 1) inhibition cellular absence extracellular sodium dicarboxylic alpha-ketoglutarate (alpha-KG; 1 mM) organic anion p-aminohippurate (PAH; mM); 2) stimulation alpha-KG (10 or PAH (1 presence an inwardly directed gradient; 3) lack sensitivity toward lithium BLPM vesicles; 4) trans-stimulation vesicular PAH, but not benzoate; 5) cis-inhibition alpha-KG/alpha-KG self-exchange extravesicular (400 (5 mM), probenecid, DIDS. Collectively, these data indicate Na(+)-dicarboxylate cotransport-coupled exchanger hepatocyte be involved liver.(ABSTRACT TRUNCATED AT 250 WORDS)