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Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain

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Noé, Birgitta, Hagenbuch, Bruno, Stieger, Bruno, Meier, Peter J.·1997·Proceedings of the National Academy of Sciences

Abstract

A novel multispecific organic anion transporting polypeptide (oatp2) has been isolated from rat brain. The cloned cDNA contains 3,640 bp. The coding region extends over 1,983 nucleotides, thus encoding a polypeptide of 661 amino acids. Oatp2 is homologous to other members of the oatp gene family of membrane transporters with 12 predicted transmembrane domains, five potential glycosylation, and six potential protein kinase C phosphorylation sites. In functional expression studies in Xenopus laevis oocytes, oatp2 mediated uptake of the bile acids taurocholate ( K m ≈ 35 μM) and cholate ( K m ≈ 46 μM), the estrogen conjugates 17β-estradiol-glucuronide ( K m ≈ 3 μM) and estrone-3-sulfate ( K m ≈ 11 μM), and the cardiac gylcosides ouabain ( K m ≈ 470 μM) and digoxin ( K m ≈ 0.24 μM). Although most of the tested compounds are common substrates of several oatp-related transporters, high-affinity uptake of digoxin is a unique feature of the newly cloned oatp2. On the basis of Northern blot analysis under high-stringency conditions, oatp2 is highly expressed in brain, liver, and kidney but not in heart, spleen, lung, skeletal muscle, and testes. These results provide further support for the overall significance of oatps as a new family of multispecific organic anion transporters. They indicate that oatp2 may play an especially important role in the brain accumulation and toxicity of digoxin and in the hepatobiliary and renal excretion of cardiac glycosides from the body.

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Metadata

Authors
Noé, B., Hagenbuch, B., Stieger, B., & Meier, P. J.
Venue
Proceedings of the National Academy of Sciences
Published
1997-09-16
Volume
94
Issue
19
Pages
10346-10350
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2088776629
Cited by
396
References
22
FWCI
12.89
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain. https://app.cochat.ai/papers/10.1073/pnas.94.19.10346
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Noé, B., Hagenbuch, B., Stieger, B., & Meier, P. J. (1997). Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.94.19.10346

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