Liver, Pancreas, and Biliary TractOrganic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver☆☆
Section snippets
Materials
All chemicals were of the highest degree of purity available and were readily available from commercial sources. [35S]BSP was synthesized at a specific activity of 9 Ci/mmol as described previously.19 [3H]Estrone-3-sulfate (53 Ci/mmol), [3H]estradiol-17β-glucuronide (44 Ci/mmol), [3H]dehydroepiandrosterone sulfate (DHEAS; 60 Ci/mmol), [3H]deltorphin II (41Ci/mmol), [3H]digoxin (19 Ci/mmol), [3H]enkephalin(2-d-penicillamin, 5-d-penicillamin; 45 Ci/mmol), [3H]ouabain (16.5 Ci/mmol), [3
Results
The full-length OATP-B cDNA coding for a 709–amino acid protein was isolated from a human brain cDNA library and contained a single serine (S)–to–phenylalanine (F) amino acid substitution at position 486 compared with the sequence published by Nagase et al.20 This substitution was also found by Tamai et al.18 The OATP-C and OATP8 cDNAs were isolated from a human liver cDNA library. Compared with the OATP-C sequence published by Abe et al.,14 there was a single asparagine (N)–to–aspartate (D)
Discussion
In this study we investigated the tissue distribution and hepatocellular localization of OATP-B, a novel member of the organic anion-transporting polypeptide family, and compared its spectrum of transport substrates with those of OATP-A, OATP-C, and OATP8 using a panel of 16 substrates previously shown to be transported by either OATP-A or by any of the rat Oatps. Northern blot analyses showed the highest level of OATP-B expression in liver, with additional expression in spleen, placenta, lung,
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Supported by grants 32-59155.99 (to G.A.K.-U.), 31-59204.99 (to B.H.), and 31-045536.95 (to P.J.M.) from the Swiss National Science Foundation, Bern, Switzerland; grant KU 899/5-2 from the Deutsche Forschungsgemeinschaft, Bonn, Germany; and grant 99B30 from the Novartis Foundation for Biomedical Research, Basel, Switzerland.
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