Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver

Gerd A. Kullak-Ublick, Bruno Hagenbuch, Bruno Stieger, Claudio D. Schteingart, Alan F. Hofmann, Allan W. Wolkoff, Peter J. Meier

Research output: Contribution to journalArticle

350 Scopus citations

Abstract

Background & Aims: Based on a recently cloned rat liver organic anion transporter, we attempted to clone the corresponding human liver organic anion transporting polypeptide. Methods: A human liver complementary DNA library was screened with a specific rat liver complementary DNA probe. The human liver transporter was cloned by homology with the rat protein and functionally characterized in Xenopus laevis oocytes. Results: The cloned human liver organic anion transporting polypeptide consists of 670 amino acids and shows a 67% amino acid identity with the corresponding rat liver protein. Injection of in vitro transcribed complementary RNA into frog oocytes resulted in the expression of sodium-independent uptake of [35S]bromosulfophthalein (Michaelis constant [Km], ∼20 μmol/L), [3H]cholate (Km, ∼93 μmol/L), [3H]taurocholate (Km, ∼60 μmol/L), [14C]glycocholate, [3H]taurochenodeoxycholate, and [3H]tauroursodeoxycholate (Km ∼19 μmol/L). Northern blot analysis showed cross-reactivity with messenger RNA species from human liver, brain, lung, kidney, and testes. Polymerase chain reaction analysis of genomic DNA from a panel of human-rodent somatic cell hybrids mapped the cloned human organic anion transporter to chromosome 12. Conclusions: These studies show that the cloned human liver organic anion transporter is closely related to, but probably not identical to, the previously cloned rat liver transporter. Furthermore, its additional localization in a variety of extrahepatic tissues suggests that it plays a fundamental role in overall transepithelial organic anion transport of the human body.

Original languageEnglish (US)
Pages (from-to)1274-1282
Number of pages9
JournalGastroenterology
Volume109
Issue number4
DOIs
StatePublished - Oct 1995

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Kullak-Ublick, G. A., Hagenbuch, B., Stieger, B., Schteingart, C. D., Hofmann, A. F., Wolkoff, A. W., & Meier, P. J. (1995). Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver. Gastroenterology, 109(4), 1274-1282. https://doi.org/10.1016/0016-5085(95)90588-X