Role of chloride and intracellular pH on the activity of the rat hepatocyte organic anion transporter

Albert D. Min, Kirsten L. Johansen, Celeste G. Campbell, Allan W. Wolkoff

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

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 CT- 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 35S-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- (Ka = 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.

Original languageEnglish (US)
Pages (from-to)1496-1502
Number of pages7
JournalJournal of Clinical Investigation
Volume87
Issue number5
DOIs
Publication statusPublished - May 1991

    Fingerprint

Keywords

  • Albumin binding
  • Chloride transport
  • Cultured hepatocytes
  • Sulfobromophthalein
  • Transport

ASJC Scopus subject areas

  • Medicine(all)

Cite this