WordNet

simple and healthful and close to nature; "an organic lifestyle"
a fertilizer that is derived from animal or vegetable matter (同)organic fertilizer, organic fertiliser
being or relating to or derived from or having properties characteristic of living organisms; "organic life"; "organic growth"; "organic remains found in rock"
involving or affecting physiology or bodily organs; "an organic disease"
of or relating to foodstuff grown or raised without synthetic fertilizers or pesticides or hormones; "organic eggs"; "organic vegetables"; "organic chicken"
relating or belonging to the class of chemical compounds having a carbon basis; "hydrocarbons are organic compounds"
move something or somebody around; usually over long distances
an exchange of molecules (and their kinetic energy and momentum) across the boundary between adjacent layers of a fluid or across cell membranes
move while supporting, either in a vehicle or in ones hands or on ones body; "You must carry your camping gear"; "carry the suitcases to the car"; "This train is carrying nuclear waste"; "These pipes carry waste water into the river" (同)carry
transport commercially (同)send, ship
wind instrument whose sound is produced by means of pipes arranged in sets supplied with air from a bellows and controlled from a large complex musical keyboard (同)pipe_organ
a fully differentiated structural and functional unit in an animal that is specialized for some particular function
a government agency or instrument devoted to the performance of some specific function; "The Census Bureau is an organ of the Commerce Department"
a periodical that is published by a special interest group; "the organ of the communist party"
a long truck for carrying motor vehicles (同)car transporter
a crane for moving material with dispatch as in loading and unloading ships
a negatively charged ion

PrepTutorEJDIC

有機体の,生物の,生物から生じた / (動植物の)器官の / 有機肥料を用いる(を用いて育った)・有機的な,組織的な,系統的な・有機質の
(ある場所からある場所へ)…‘を'『輸送する』,運搬する《+名+from+名+to+名》 / 《文》《受動態で》(…で)…‘を'夢中にする,有頂天にする《+名+with+名》 / 〈罪人〉‘を'流刑にする / 〈U〉輸送,運送,輸送(交通)機関(transportation) / 〈C〉(軍隊や軍需品を運ぶ)輸送船,輸送機
『オルガン』,パイプオルガン(pipe organ),リードオルガン(reed organ),電子オルガン(electronic organ),手回しオルガン(barrel organ) / (動植物の)『器官』 / (政党・会社などの)機関誌,機関紙 / 《しばしば複数形で》(行動・実施などの)組織,機関
自動車運搬用大型トラック
陰イオン

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/31 15:47:19」(JST)

wiki en

An organic anion-transporting polypeptide (OATP) is a membrane transport protein or 'transporter' that mediates the transport of mainly organic anions across the cell membrane. Therefore OATPs are present in the lipid bilayer of the cell membrane, acting as the cell's gatekeepers. OATPs belong to the Solute Carrier Family (SLC), more specifically the Solute Carrier Organic Anion (SLCO) gene subfamily ^[1]

Function

Organic anion transporting polypeptides carry bile acids as well as bilirubin and numerous hormones such as thyroid and steroid hormones across the basolateral membrane (facing sinusoids) in hepatocytes, for excretion in bile.^[2] As well as expression in the liver, OATPs are expressed in many other tissues on basolateral and apical membranes, transporting anions, as well as neutral and even cationic compounds. They also transport an extremely diverse range of drug compounds, ranging from anti-cancer, antibiotic, lipid lowering to anti-diabetic drugs, as well as toxins and poisons.

Various anti-cancer drugs like pazopanib, vandetanib, nilotinib, canertinib and erlotinib are known to be transported via OATPs (OATP-1B1 and OATP-1B3).^[3]

Also, anti-cancer drugs specially the tyrosine kinase inhibitors have been reported as inhibitors of OATP (OATP-1B1 and OATP-1B3. Pazopanib and Nilotinib have shown their inhibitory potential only towards OATP-1B1 but not towards OATP-1B3 whereas Vandetanib has shown its inhibitory activity only towards OATP-1B3 but not towards OATP-1B1.^[4]

They also transport the dye bromosulphopthalein, availing it as a liver-testing substance.^[2]

Proteins

The table below shows the 11 known human OATPs. Note: Human OATPs are designated with capital letters, animal Oatps are designated with lower class letters. The 'SLCO' stands for their gene name; 'solute carrier organic anion.' Previous nomenclature using letters and numbers (e.g. OATP-A, OATP-8 is no longer correct. The most well characterised human OATPs are OATP1A2, OATP1B1, OATP1B3 and OATP2B1. Very little is known about the function and characteristics of OATP5A1 and OATP6A1.

Abbreviation	Protein Name	Location
SLCO1A2	Solute carrier organic anion transporter family member 1A2	Ubiquitous
SLCO1B1	Solute carrier organic anion transporter family member 1B1	Liver
SLCO1B3	Solute carrier organic anion transporter family member 1B3	Liver
SLCO1C1	Solute carrier organic anion transporter family member 1C1	Brain, testis
SLCO2A1	Solute carrier organic anion transporter family member 2A1	Ubiquitous
SLCO2B1	Solute carrier organic anion transporter family member 2B1	Ubiquitous
SLCO3A1	Solute carrier organic anion transporter family member 3A1	Testis, brain, heart, lung, spleen
SLCO4A1	Solute carrier organic anion transporter family member 4A1	Heart, placenta, lung, liver
SLCO4C1	Solute carrier organic anion transporter family member 4C1	Kidney
SLCO5A1	Solute carrier organic anion transporter family member 5A1	Breast, fetal brain, prostate
SLCO6A1	Solute carrier organic anion transporter family member 6A1	Testes, spleen, brain, placenta

Pharmacology

The OATPs play a role in the transport of some classes of drugs across the cell membrane, particularly in the liver and kidney. In the liver, OATPs are expressed on the basolateral membrane of hepatocytes, transporting compounds into the hepatocyte for biotransformation. A number of drug-drug interactions have been associated with the OATPs, affecting the pharmacokinetics and pharmacodynamics of drugs. This is most commonly where one drug inhibits the transport of another drug into the hepatocyte, so that it is retained longer in the body (i.e. increased plasma half-life). The OATPs most associated with these interactions are OATP1B1, OATP1B3 and OATP2B1, which are all present on the hepatocyte basolateral (sinusoidal) membrane. OATP1B1 and OATP1B3 are known to play an important role in hepatic drug disposition. These OATPs contribute towards first step of hepatic accumulation and can influence the disposition of drug via hepatic route.^[3] The most clinically relevant interactions have been associated with the lipid lowering drugs statins, which led to the removal of cerivastatin from the market in 2002. Single nucleotide polymorphisms (SNPs) are also associated with the OATPs; particularly OATP1B1.

Many modulators of OATP function have been identified based on in vitro research in OATP-transfected cell lines.^[5]^[6] Both OATP activation and inhibition has been observed and an in silico model for structure-based identification of OATP modulation was developed.^[7]

Since tyrosine kinase inhibitors (TKIs) are metabolized in the liver, interaction of TKIs with OATP1B1 and OATP1B3 can be considered as important molecular targets for transporter mediated drug-drug interactions.^[3]

Along with the organic anion transporters, organic cation transporters and the ATP-binding cassette transporters, the OATPs play an important role in the absorption, distribution, metabolism and exretion (ADME) of many drugs.

Evolution

OATPs are present in many animals, including fruit flies, zebrafish, dogs, cows, rats, mice, monkeys and horses. OATPs are not present in bacteria, indicating their evolution from the animal kingdom. However homologs do not correlate well with the human OATPs and therefore it is likely that isoforms arose by gene duplication. OATPs have however been found in insects,^[8] suggesting that their evolution was early in the formation of the animal kingdom.

References

^ Hagenbuch B, Meier PJ (February 2004). "Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties". Pflugers Arch. 447 (5): 653–65. doi:10.1007/s00424-003-1168-y. PMID 14579113.
^ ^a ^b Pages 980-990 in:Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1300. ISBN 1-4160-2328-3.
^ ^a ^b ^c Khurana V, Minocha M, Pal D, Mitra AK (March 2014). "Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors.". Drug Metabol Drug Interact. 0 (3): 1–11. doi:10.1515/dmdi-2013-0062. PMID 24643910.
^ Khurana V, Minocha M, Pal D, Mitra AK (May 2014). "Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors.". Drug Metabol Drug Interact. 0 (4): 1–11. doi:10.1515/dmdi-2014-0014. PMID 24807167.
^ Annaert P, Ye ZW, Stieger B, Augustijns P. Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1" Xenobiotica 2010 Mar;40(3):163-76. doi: 10.3109/00498250903509375. PMID 20102298.
^ De Bruyn, T; Fattah, S; Stieger, B; Augustijns, P; Annaert, P (Nov 2011). "Sodium fluorescein is a probe substrate for hepatic drug transport mediated by OATP1B1 and OATP1B3". J Pharm Sci. 100 (11): 5018–30. doi:10.1002/jps.22694. PMID 21837650.
^ De Bruyn, T; van Westen, GJ; Ijzerman, AP; Stieger, B; de Witte, P; Augustijns, PF; Annaert, PP (Jun 2013). "Structure-based identification of OATP1B1/3 inhibitors". Mol Pharmacol 83 (6): 1257–67. doi:10.1124/mol.112.084152. PMID 23571415.
^ Torrie LS, Radford JC, Southall TD, Kean L, Dinsmore AJ, Davies SA, Dow JA (2004-09-07). "Resolution of the insect ouabain paradox". PNAS 101 (37): 13689–93. doi:10.1073/pnas.0403087101.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. Chapter 3C：近位尿細管における分泌経路 chapter 3c secretory pathways in proximal tubule
2. 尿酸のバランス uric acid balance
3. Chapter 3B：近位尿細管におけるナトリウム輸送能の優越性 chapter 3b primacy of sodium transport in proximal function
4. スタチン誘発性ミオパチー statin myopathy
5. 先天性代謝異常：代謝性救急疾患 inborn errors of metabolism metabolic emergencies

English Journal

In vivo selective imaging and inhibition of leukemia stem-like cells using the fluorescent carbocyanine derivative, DiOC5(3).

Zhang B1, Shimada Y2, Kuroyanagi J1, Ariyoshi M1, Nomoto T3, Shintou T3, Umemoto N4, Nishimura Y2, Miyazaki T3, Tanaka T5.
Biomaterials.Biomaterials.2015 Jun;52:14-25. doi: 10.1016/j.biomaterials.2015.02.009. Epub 2015 Feb 21.
Elimination of leukemia stem cells (LSCs) is necessary for the destruction of malignant cell populations. Owing to the very small number of LSCs in leukemia cells, xenotransplantation studies are difficult in terms of functionally and pathophysiologically replicating clinical conditions of cell cult
PMID 25818410

Gene replacement therapy for genetic hepatocellular jaundice.

van Dijk R1, Beuers U, Bosma PJ.
Clinical reviews in allergy & immunology.Clin Rev Allergy Immunol.2015 Jun;48(2-3):243-53. doi: 10.1007/s12016-014-8454-7.
Jaundice results from the systemic accumulation of bilirubin, the final product of the catabolism of haem. Inherited liver disorders of bilirubin metabolism and transport can result in reduced hepatic uptake, conjugation or biliary secretion of bilirubin. In patients with Rotor syndrome, bilirubin (
PMID 25315738

Evaluation of cynomolgus monkeys for the identification of endogenous biomarkers for hepatic transporter inhibition and as a translatable model to predict pharmacokinetic interactions with statins in humans.

Chu X1, Shih SJ2, Shaw R2, Hentze H2, Chan GH2, Owens K2, Wang S2, Cai X2, Newton D2, Castro-Perez J2, Salituro G2, Palamanda J2, Fernandis A2, Ng CK2, Liaw A2, Savage MJ2, Evers R2.
Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2015 Jun;43(6):851-63. doi: 10.1124/dmd.115.063347. Epub 2015 Mar 26.
Inhibition of hepatic transporters such as organic anion transporting polypeptides (OATPs) 1B can cause drug-drug interactions (DDIs). Determining the impact of perpetrator drugs on the plasma exposure of endogenous substrates for OATP1B could be valuable to assess the risk for DDIs early in drug de
PMID 25813937

Japanese Journal

The expression of transporter OATP2/OATP8 decreases in undetectable hepatocellular carcinoma by Gd-EOB-MRI in the explanted cirrhotic liver

Hidaka Masaaki,Takatsuki Mitsuhisa,Okudaira Sadayuki,Soyama Akihiko,Muraoka Izumi,Tanaka Takayuki,Yamaguchi Izumi,Hara Takanobu,Miyaaki Hisamitsu,Ichikawa Tatsuki,Hayashi Tomayoshi,Sakamoto Ichiro,Nakao Kazuhiko,Kuroki Tamotsu,Kanematsu Takashi,Eguchi Susumu
Hepatology International 7(2), 655-661, 2013-06-00
… Purpose: The aim of this study is to evaluate the detectability of hepatocellular carcinoma (HCC) in the explanted cirrhotic liver using gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) and the degree of organic anion transporter OATP2/OATP8 (OATP1B1/1B3) HCC which could not be preoperatively detected by multi-detector computed tomography (MD-CT) and Gd-EOB-MRI. … The transporter of OATP2/OATP8 was less expressed in the preoperatively undetectable HCCs. …
NAID 120005311953

Sustained Repression and Translocation of NTCP and Expression of MRP4 for Cholestasis after Rat 90% Partial Hepatectomy

Miura Takuya,Kimura Norihisa,Yamada Toshiyuki,Shimizu Takeshi,Nanashima Naoki,Yamana Daisuke,Hakamada Kenichi,Tsuchida Shigeki
弘前医学 64(Supplement), S99-S106, 2013-04-02
… Background/Aims: To clarify the mechanism of persistent cholestasis after massive hepatectomy, the relationship between such cholestasis and the expression and localization of organic anion transporters for bile acids was examined in a rat model.Methods: Male Sprague-Dawley rats were subjected to 90% hepatectomy, and tissues were harvested on 0, 1, 3, and 7 days for microarray analysis, the quantitative real-time polymerase chain reaction （RT-PCR）, Western blotting and immunohistochemistry to examine the expression of …
NAID 120005230059

Active intestinal absorption of fluoroquinolone antibacterial agent ciprofloxacin by organic anion transporting polypeptide, Oatp1a5

Arakawa Hiroshi,Shirasaka Yoshiyuki,Haga Makoto,Nakanishi Takeo,Tamai Ikumi
Biopharmaceutics and Drug Disposition 33(6), 332-341, 2012-09-00
… It has been that several fluoroquinolones are substrates of organic anion transporter polypeptides OATP1A2 expressed in human intestine derived Caco-2 cells. …
NAID 120004997009

Related Pictures

★リンクテーブル★

リンク元	「有機アニオントランスポーター」「OAT」
拡張検索	「canalicular multispecific organic anion transporter」「sodium-dependent organic anion transporter」「organic anion transporter 2」「organic anion transporters」
関連記事	「transport」「organic」「anion transporter」「transporter」「ani」

「有機アニオントランスポーター」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Organic Anion Transporter Polypeptide (OATP) family
Identifiers
Symbol	OATP
Pfam	PF03137
InterPro	IPR004156
TCDB	2.A.60
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

　　[★]

英: organic anion transporter, OAT、organic anion transporters, OATs
同: 有機アニオン輸送体

[show details]

有機アニオントランスポーター : 約 11,400 件
有機アニオン輸送体 : 84 件

「OAT」

　　[★] 有機アニオントランスポーター organic anion transporter

「canalicular multispecific organic anion transporter」

　　[★]

胆管側多選択性有機アニオントランス・ーター、胆管側多選択性有機アニオン輸送体

関: cMOAT

「sodium-dependent organic anion transporter」

　　[★]

ナトリウム依存性有機アニオントランス・ーター、ナトリウム依存性有機アニオン輸送体

「organic anion transporter 2」

　　[★]

有機アニオン輸送体2、有機アニオントランスポーター2

「organic anion transporters」

　　[★] 有機アニオントランスポーター OATs

「transport」

　　[★]

n.

輸送、運搬

v.

輸送する、運搬する、運ぶ

関: bring、carriage、carry、convey、delivery、ship、traffic、trafficking、transportation

「organic」

　　[★]

adj.

有機物の、有機の、有機的な、器質性の、器質的な

関: organic compound、organic matter、organized、organo

「anion transporter」

　　[★]

アニオン輸送体、アニオントランス・ーター、陰イオン輸送体

関: anion transport protein

「transporter」

　　[★] トランスポーター

関: translocator、transport protein、transporter protein

「ani」

　　[★]

np

肛門

関: anal、anus

[Hagenbuch_2004b-1] Hagenbuch B, Meier PJ (February 2004). "Organic anion transporting polypeptides of the OATP/ SLC21 family: phylogenetic classification as OATP/ SLCO superfamily, new nomenclature and molecular/functional properties". Pflugers Arch. 447 (5): 653–65. doi:10.1007/s00424-003-1168-y. PMID 14579113.

[boron990-2] Pages 980-990 in:Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1300. ISBN 1-4160-2328-3.

[Khurana_2014-3] Khurana V, Minocha M, Pal D, Mitra AK (March 2014). "Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors.". Drug Metabol Drug Interact. 0 (3): 1–11. doi:10.1515/dmdi-2013-0062. PMID 24643910.

[Khurana_V_2014-4] Khurana V, Minocha M, Pal D, Mitra AK (May 2014). "Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors.". Drug Metabol Drug Interact. 0 (4): 1–11. doi:10.1515/dmdi-2014-0014. PMID 24807167.

[5] Annaert P, Ye ZW, Stieger B, Augustijns P. Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1" Xenobiotica 2010 Mar;40(3):163-76. doi: 10.3109/00498250903509375. PMID 20102298.

[6] De Bruyn, T; Fattah, S; Stieger, B; Augustijns, P; Annaert, P (Nov 2011). "Sodium fluorescein is a probe substrate for hepatic drug transport mediated by OATP1B1 and OATP1B3". J Pharm Sci. 100 (11): 5018–30. doi:10.1002/jps.22694. PMID 21837650.

[7] De Bruyn, T; van Westen, GJ; Ijzerman, AP; Stieger, B; de Witte, P; Augustijns, PF; Annaert, PP (Jun 2013). "Structure-based identification of OATP1B1/3 inhibitors". Mol Pharmacol 83 (6): 1257–67. doi:10.1124/mol.112.084152. PMID 23571415.

[pnas13689-8] Torrie LS, Radford JC, Southall TD, Kean L, Dinsmore AJ, Davies SA, Dow JA (2004-09-07). "Resolution of the insect ouabain paradox". PNAS 101 (37): 13689–93. doi:10.1073/pnas.0403087101.

匿名

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案内

案内

organic anion transporter