Molecular Cloning and Characterization of a New Multispecific Organic Anion Transporter from Rat Brain

Kusuhara, Hiroyuki; Sekine, Takashi; Utsunomiya‐Tate, Naoko; Tsuda, Minoru; Kojima, Ryoji; Ho, Seok; Sugiyama, Yuichi; Kanai, Yoshikatsu; Endou, Hitoshi

doi:10.1074/jbc.274.19.13675

Cited by 440 publications

(504 citation statements)

References 25 publications

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“…Besides OAT2, rat OAT3, expressed in the liver, kidney, and brain, mediates the transport of [ 3 H]ES. 38 However, its human and murine orthologs hOAT3/mOat3 are not expressed in the liver. 26,39 OAT7 is, thus, the first liver-specific functional OAT member found in humans.…”

Section: Discussionmentioning

confidence: 99%

Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate

et al. 2007

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The liver plays an important role in the elimination of endogenous and exogenous lipophilic organic compounds from the body, which is mediated by various carrier proteins that differ in substrate specificity and kinetic properties. Here, we have characterized a novel member of the organic anion transporter family (SLC22) isolated from human liver. The transporter named organic anion transporter 7 (OAT7/ SLC22A9) showed 35% to 46% identities to those of other organic anion transporters of SLC22 family. When expressed in Xenopus oocytes, OAT7 mediated Na ؉ -independent, highaffinity transport of sulfate-conjugated steroids, estrone sulfate (ES; K m ‫؍‬ 8.7 M), and dehydroepiandrosterone sulfate (K m ‫؍‬ 2.2 M). In addition, OAT7 interacted with negatively charged sulfobromophthalein, indocyanine green, and several sulfate-conjugated xenobiotics. In contrast, glucuronide and glutathione conjugates exhibited no inhibitory effects on OAT7-mediated

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Section: Discussionmentioning

confidence: 99%

Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate

et al. 2007

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“…several other species, including mice, rabbits, pigs and humans, and can exhibit substantial amino acid divergence ($78% identity between mouse and human) [52,67,68]. Oat3/OAT3 mRNA has been identified in the blood-brain barrier endothelium, the lining of ventricles in the brain (choroid plexus) and kidney [52,[66][67][68]. Oat3 mRNA has also been found in rat liver, albeit at relatively low levels; however, hepatic expression was not observed in mice [52,56,64,65].…”

Section: Oat2 (Slc22a7)mentioning

confidence: 99%

Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology

VanWert

Gionfriddo

Sweet

2009

Biopharm & Drug Disp

219

238

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Our understanding of the mechanisms behind inter-and intra-patient variability in drug response is inadequate. Advances in the cytochrome P450 drug metabolizing enzyme field have been remarkable, but those in the drug transporter field have trailed behind. Currently, however, interest in carrier-mediated disposition of pharmacotherapeutics is on a substantial uprise. This is exemplified by the 2006 FDA guidance statement directed to the pharmaceutical industry. The guidance recommended that industry ascertain whether novel drug entities interact with transporters. This suggestion likely stems from the observation that several novel cloned transporters contribute significantly to the disposition of various approved drugs. Many drugs bear anionic functional groups, and thus interact with organic anion transporters (OATs). Collectively, these transporters are nearly ubiquitously expressed in barrier epithelia. Moreover, several reports indicate that OATs are subject to diverse forms of regulation, much like drug metabolizing enzymes and receptors. Thus, critical to furthering our understanding of patient-and condition-specific responses to pharmacotherapy is the complete characterization of OAT interactions with drugs and regulatory factors. This review provides the reader with a comprehensive account of the function and substrate profile of cloned OATs. In addition, a major focus of this review is on the regulation of OATs including the impact of transcriptional and epigenetic factors, phosphorylation, hormones and gender.

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“…The organic anion and urate transporters OAT1 (SLC22A6) and OAT3 (SLC22A8) can function as urate/ dicarboxylate exchangers (61)(62)(63)(64) and are found on the basolateral side of the same cells that express Oat4 (58). However, Oat3 is also found in all segments of the rat nephron from the proximal tubule to the collecting duct (65).…”

Section: Figurementioning

confidence: 99%

Uric acid transport and disease

Thorens²

2010

J. Clin. Invest.

669

496

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Uric acid is the metabolic end product of purine metabolism in humans. It has antioxidant properties that may be protective but can also be pro-oxidant, depending on its chemical microenvironment. Hyperuricemia predisposes to disease through the formation of urate crystals that cause gout, but hyperuricemia, independent of crystal formation, has also been linked with hypertension, atherosclerosis, insulin resistance, and diabetes. We discuss here the biology of urate metabolism and its role in disease. We also cover the genetics of urate transport, including URAT1, and recent studies identifying SLC2A9, which encodes the glucose transporter family isoform Glut9, as a major determinant of plasma uric acid levels and of gout development.Conflict of interest: Alexander So has acted as a consultant and advisor for Novartis.Citation for this article:

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Molecular Cloning and Characterization of a New Multispecific Organic Anion Transporter from Rat Brain

Cited by 440 publications

References 25 publications

Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate

Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate

Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology

Uric acid transport and disease

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