{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670319502024960.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.1033060100"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.1033060100"}}],"dc:title":[{"@value":"The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>\n            Prostaglandins are involved in a wide variety of physiological and\n pathophysiological processes, but the mechanism of prostaglandin release from\n cells is not completely understood. Although poorly membrane permeable,\n prostaglandins are believed to exit cells by passive diffusion. We have\n investigated the interaction between prostaglandins and members of the\n ATP-binding cassette (ABC) transporter ABCC [multidrug resistance protein\n (MRP)] family of membrane export pumps. In inside-out membrane vesicles\n derived from insect cells or HEK293 cells, MRP4 catalyzed the time- and\n ATP-dependent uptake of prostaglandin E\n            <jats:sub>1</jats:sub>\n            (PGE\n            <jats:sub>1</jats:sub>\n            ) and\n PGE\n            <jats:sub>2</jats:sub>\n            . In contrast, MRP1, MRP2, MRP3, and MRP5 did not transport\n PGE\n            <jats:sub>1</jats:sub>\n            or PGE\n            <jats:sub>2</jats:sub>\n            . The MRP4-mediated transport of\n PGE\n            <jats:sub>1</jats:sub>\n            and PGE\n            <jats:sub>2</jats:sub>\n            displayed saturation kinetics, with\n            <jats:italic>K</jats:italic>\n            <jats:sub>m</jats:sub>\n            values of 2.1 and 3.4 μM, respectively. Further\n studies showed that PGF\n            <jats:sub>1</jats:sub>\n            <jats:sub>α</jats:sub>\n            ,\n PGF\n            <jats:sub>2</jats:sub>\n            <jats:sub>α</jats:sub>\n            , PGA\n            <jats:sub>1</jats:sub>\n            , and thromboxane\n B\n            <jats:sub>2</jats:sub>\n            were high-affinity inhibitors (and therefore presumably\n substrates) of MRP4. Furthermore, several nonsteroidal antiinflammatory drugs\n were potent inhibitors of MRP4 at concentrations that did not inhibit MRP1. In\n cells expressing the prostaglandin transporter PGT, the steady-state\n accumulation of PGE\n            <jats:sub>1</jats:sub>\n            and PGE\n            <jats:sub>2</jats:sub>\n            was reduced proportional\n to MRP4 expression. Inhibition of MRP4 by an MRP4-specific RNA interference\n construct or by indomethacin reversed this accumulation deficit. Together,\n these data suggest that MRP4 can release prostaglandins from cells, and that,\n in addition to inhibiting prostaglandin synthesis, some nonsteroidal\n antiinflammatory drugs might also act by inhibiting this release.\n          </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380294645962742402","@type":"Researcher","foaf:name":[{"@value":"Glen Reid"}],"jpcoar:affiliationName":[{"@value":"Division of Molecular Biology and Center of Biomedical Genetics, The\r Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The\r Netherlands"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294645962742400","@type":"Researcher","foaf:name":[{"@value":"Peter Wielinga"}],"jpcoar:affiliationName":[{"@value":"Division of Molecular Biology and Center of Biomedical Genetics, The\r Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The\r Netherlands"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294645962742407","@type":"Researcher","foaf:name":[{"@value":"Noam Zelcer"}],"jpcoar:affiliationName":[{"@value":"Division of Molecular Biology and Center of Biomedical Genetics, The\r Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The\r Netherlands"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294645962742403","@type":"Researcher","foaf:name":[{"@value":"Ingrid van der Heijden"}],"jpcoar:affiliationName":[{"@value":"Division of Molecular Biology and Center of Biomedical Genetics, The\r Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The\r Netherlands"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294645962742401","@type":"Researcher","foaf:name":[{"@value":"Annemieke Kuil"}],"jpcoar:affiliationName":[{"@value":"Division of Molecular Biology and Center of Biomedical Genetics, The\r Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The\r Netherlands"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294645962742406","@type":"Researcher","foaf:name":[{"@value":"Marcel de Haas"}],"jpcoar:affiliationName":[{"@value":"Division of Molecular Biology and Center of Biomedical Genetics, The\r Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The\r Netherlands"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294645962742404","@type":"Researcher","foaf:name":[{"@value":"Jan Wijnholds"}],"jpcoar:affiliationName":[{"@value":"Division of Molecular Biology and Center of Biomedical Genetics, The\r Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The\r Netherlands"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294645962742405","@type":"Researcher","foaf:name":[{"@value":"Piet Borst"}],"jpcoar:affiliationName":[{"@value":"Division of Molecular Biology and Center of Biomedical Genetics, The\r Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The\r Netherlands"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2003-06-30","prism:volume":"100","prism:number":"16","prism:startingPage":"9244","prism:endingPage":"9249"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.1033060100"}],"createdAt":"2003-08-05","modifiedAt":"2022-04-12","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050865187562977024","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Calcium transients trigger switch-like discharge of prostaglandin E2 in an extracellular signal-regulated kinase-dependent manner"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004232305660288","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Gene Expression Analysis of Membrane Transport Proteins in Normal and 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Membrane"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001205181245056","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Transporter-mediated Prostaglandin E<sub>2</sub> Elimination across the Rat Blood-brain Barrier and Its Attenuation by the Activation of N-methyl-D-aspartate Receptors"},{"@value":"Transporter-mediated Prostaglandin E2 Elimination across the Rat Blood-brain Barrier and Its Attenuation by the Activation of N-methyl-D-aspartate Receptors"}]},{"@id":"https://cir.nii.ac.jp/crid/1390016902825832832","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Visual quantification of prostaglandin E<sub>2</sub> discharge from a single cell"},{"@value":"Visual quantification of prostaglandin E₂ discharge from a single cell"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282681103187072","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"プロスタグランジン類の膜輸送に係わる新規ヒト型輸送担体（Human Prostaglandin Carrier, hPrC）の単離と機能の特定"},{"@language":"en","@value":"Molecular Cloning and Functional Characterization of a Novel Gene Encoding Human Prostaglandin Carrier, hPrC"},{"@language":"ja-Kana","@value":"プロスタグランジンルイ ノ マク ユソウ ニ カカワル シンキ ヒトガタ ユソウ タンタイ Human Prostaglandin Carrier hPrC ノ タンリ ト キノウ ノ トクテイ"}]},{"@id":"https://cir.nii.ac.jp/crid/1390286426514760448","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Inflammation-Induced Attenuation of Prostaglandin D<sub>2</sub> Elimination across Rat Blood–Brain Barrier: Involvement of the Downregulation of Organic Anion Transporter 3 and Multidrug Resistance-Associated Protein 4"},{"@value":"Inflammation-Induced Attenuation of Prostaglandin D₂ 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