Molecular Identification of a Rat Novel Organic Anion Transporter moat1, Which Transports Prostaglandin D2, Leukotriene C4, and Taurocholate

Nishio, Takeshi; Adachi, Hisanobu; Nakagomi, Rie; Tokui, Taro; Satô, Eiichi; Tanemoto, Masayuki; Fujiwara, Kimiko; Okabe, Mitsunori; Onogawa, Tohru; Suzuki, Takehiro; Nakai, Daisuke; Shiiba, Kenici; Suzuki, Masanori; Ohtani, Haruo; Kondo, Yoshiaki; Unno, Michiaki; Ito, Sadayoshi; Iinuma, Kazuie; Nunoki, Kazuo; Matsuno, Seiki; Abe, Takaaki

doi:10.1006/bbrc.2000.3377

Cited by 67 publications

(22 citation statements)

References 39 publications

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“…However, amino acid sequence identity between OATP-B and Oatp3 is low (34%) (Hagenbuch and Meier, 2003) and rat Oatp3 may not be an ortholog of OATP-B; indeed, Walters et al (2000) proposed that rat Oatp3 is a homolog of OATP-A. Nishio et al (2000) cloned moat-1 from rat brain and showed that it has a higher homology (76%) with OATP-B than any other cloned human OATP (Nishio et al, 2000). However, it has not been clarified yet whether OATP-A or moat-1 is localized at the apical membrane of the small intestine.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Human Organic Anion Transporting Polypeptide OATP-B (SLC21A9) in pH-Dependent Transport across Intestinal Apical Membrane

Kobayashi

Nozawa²,

Imai³

et al. 2003

J Pharmacol Exp Ther

377

323

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Some organic anions are absorbed from the gastrointestinal tract through carrier-mediated transport mechanism(s), which may include proton-coupled transport, anion exchange transport, and others. However, the molecular identity of the organic anion transporters localized at the apical membrane of human intestinal epithelial cells has not been clearly demonstrated. In the present study, we focused on human organic anion transporting polypeptide OATP-B and examined its subcellular localization and functionality in the small intestine. Localization of OATP-B was determined by immunohistochemical analysis. Transport properties of estrone-3-sulfate and the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor pravastatin by OATP-Btransfected human embryonic kidney 293 cells were measured. OATP-B was immunohistochemically localized at the apical membrane of intestinal epithelial cells in humans. Uptake of 14 C]pravastatin by OATP-B at pH 5.5 was higher than that at pH 7.4. [3 H]Estrone-3-sulfate transport was decreased by pravastatin, aromatic anion compounds, and the anion exchange inhibitor 4,4Ј-diisothiocyanostilbene-2,2Ј-disulfonic acid, but not by small anionic compounds, such as lactic acid and acetic acid. The inhibitory effect of pravastatin on the uptake of [ 3 H]estrone-3-sulfate was concentration-dependent, and the IC 50 value was 5.5 mM. The results suggested that OATP-B mediates absorption of anionic compounds and its activity may be optimum at the acidic surface microclimate pH of the small intestine. Accordingly, OATP-B plays a role in the absorption of anionic compounds across the apical membrane of human intestinal epithelial cells, although it cannot be decisively concluded that pH-dependent absorption of pravastatin is determined by OATP-B alone.

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Section: Discussionmentioning

confidence: 99%

Involvement of Human Organic Anion Transporting Polypeptide OATP-B (SLC21A9) in pH-Dependent Transport across Intestinal Apical Membrane

Kobayashi

Nozawa²,

Imai³

et al. 2003

J Pharmacol Exp Ther

377

323

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“…Oatp5 mRNA was almost exclusively expressed in kidney, with minimal expression in other tissues . Oatp9 mRNA, recently discovered as moat1 to transport taurocholate, prostaglandin D, and leukotrienes (Nishio et al, 2000), was present in placenta, however the levels were lower than in liver and kidney. Oatp12 mRNA levels, recently determined to transport thyroid hormone in various peripheral tissues (Fujiwara et al, 2001), were most abundant in placenta (Fig.…”

Section: Xenobiotic Transporters In Rat Placentamentioning

confidence: 94%

The Presence of Xenobiotic Transporters in Rat Placenta

Leazer

Klaassen²

2003

Drug Metab Dispos

113

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ABSTRACT:Understanding the role of transporters in placental handling of xenobiotics across the maternal-fetal interface is essential to evaluate the pharmacological and toxicological potential of therapeutic agents, drugs of abuse, and other xenobiotics to which the mother is exposed during pregnancy. Therefore, the purpose of this study was to assess mRNA levels of various transporters in placenta and to compare these to levels in maternal liver and kidney, predominant organs of excretion, to determine which transporters are likely to have a role in xenobiotic transfer within the placenta. During late stage pregnancy, relative amounts of mRNA levels of 40 genes representing 11 families/group of transporters were assessed in placenta with respect to relative maternal liver and kidney mRNA levels. Members of the following transporter families were assessed: three multidrug resistance (

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“…In fact, transport is the rate-limiting step of PGE 2 inactivation, at least in the lungs (4). The major carriers of PGE 2 are PG transporter (PGT; also known as matrin) and multispecific organic anion transporter (MOAT) (41,57). Intracellular catabolism of PGE 2 consists of several subsequent reactions, of which the first reaction, enzymatic oxidation of the 15-hydroxyl group, is crucial because it leads to the loss of biological activities (18).…”

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confidence: 99%

Expression of genes controlling transport and catabolism of prostaglandin E₂in lipopolysaccharide fever

Ivanov¹,

Scheck

Romanovsky³

2003

American Journal of Physiology-Regulatory, Integrative and Comp

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) E2 is a principal downstream mediator of fever and other symptoms of systemic inflammation. Its inactivation occurs in peripheral tissues, primarily the lungs and liver, via carrier-mediated cellular uptake and enzymatic oxidation. We hypothesized that inactivation of PGE2 is suppressed during LPS fever and that transcriptional downregulation of PGE2 carriers and catabolizing enzymes contributes to this suppression. Fever was induced in inbred Wistar-Kyoto rats by intravenous LPS (50 g/kg); the controls received saline. Samples of the liver, lungs, and hypothalamus were harvested 0, 0.5, 1.5, and 5 h postinjection. The expression of the two principal transmembrane PGE2 carriers (PG transporter and multispecific organic anion transporter) and the two key PGE2-inactivating enzymes [15-hydroxy-PG dehydrogenase (15-PGDH) and carbonyl reductase] was quantified by RT-PCR. All four genes of interest were downregulated in peripheral tissues (but not the brain) during fever. Most remarkably, the expression of hepatic 15-PGDH was decreased 26-fold 5 h post-LPS, whereas expression of pulmonary 15-PGDH was downregulated (as much as 18-fold) throughout the entire febrile course. The transcriptional downregulation of several proteins involved in PGE2 inactivation, first reported here, is an unrecognized mechanism of systemic inflammation. By increasing the bloodbrain gradient of PGE2, this mechanism likely facilitates penetration of PGE2 into the brain and prevents its elimination from the brain. systemic inflammation; multispecific organic anion transporter; prostaglandin transporter; 15-hydroxyprostaglandin dehydrogenase; carbonyl reductase ON A SYSTEMIC INFLAMMATORY challenge (e.g., with bacte-

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Molecular Identification of a Rat Novel Organic Anion Transporter moat1, Which Transports Prostaglandin D2, Leukotriene C4, and Taurocholate

Cited by 67 publications

References 39 publications

Involvement of Human Organic Anion Transporting Polypeptide OATP-B (SLC21A9) in pH-Dependent Transport across Intestinal Apical Membrane

Involvement of Human Organic Anion Transporting Polypeptide OATP-B (SLC21A9) in pH-Dependent Transport across Intestinal Apical Membrane

The Presence of Xenobiotic Transporters in Rat Placenta

Expression of genes controlling transport and catabolism of prostaglandin E₂in lipopolysaccharide fever

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Molecular Identification of a Rat Novel Organic Anion Transporter moat1, Which Transports Prostaglandin D2, Leukotriene C4, and Taurocholate

Cited by 67 publications

References 39 publications

Involvement of Human Organic Anion Transporting Polypeptide OATP-B (SLC21A9) in pH-Dependent Transport across Intestinal Apical Membrane

Involvement of Human Organic Anion Transporting Polypeptide OATP-B (SLC21A9) in pH-Dependent Transport across Intestinal Apical Membrane

The Presence of Xenobiotic Transporters in Rat Placenta

Expression of genes controlling transport and catabolism of prostaglandin E2in lipopolysaccharide fever

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Expression of genes controlling transport and catabolism of prostaglandin E₂in lipopolysaccharide fever