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Further insights into sinusoidal organic anion uptake
Author(s) -
Gumucio Jorge J.,
Moseley Richard H.
Publication year - 1992
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840150127
Subject(s) - sulfobromophthalein , cotransporter , hepatocyte , extracellular , chemistry , transporter , biophysics , albumin , bumetanide , ion transporter , kinetics , membrane transport , organic anion , ion , biochemistry , sodium , medicine , biology , membrane , in vitro , physics , organic chemistry , quantum mechanics , liver function tests , gene
Previous studies in cultured rat hepatocytes revealed that initial uptake of sulfobromophthalein (BSP) was markedly reduced upon removal of Cl − from the medium. In the present study, unidirectional Cl − gradients were established in short‐term cultured rat hepatocytes and their effect on BSP uptake was determined. These investigations revealed that BSP uptake requires external Cl − and is not stimulated by unidirectional Cl − gradients, suggesting that BSP transport is not coupled to Cl − transport. In contrast, BSP transport is stimulated by an inside‐to‐outside OH − gradient, consistent with OH − exchange or H + cotransport. As the presence of Cl − is essential for but not directly coupled to BSP transport, binding of 35 S‐BSP to hepatocytes was determined at 4° C. This revealed an ∼ 10‐fold higher affinity of cells for BSP in the presence as compared to the absence of Cl − (K a + 3.2 ± 0.8 vs. 0.42 ± 0.09 μM −1 ; P < 0.02). Affinity of BSP for albumin was Cl − ‐independent, and was ∼ 10% of its affinity for cells in the presence of Cl − . These results indicate that extracellular Cl − modulates the affinity of BSP for its hepatocyte transporter.