Transporters involved in the elimination of drugs in the kidney: Organic anion transporters and organic cation transporters

Dresser, Mark J.; Leabman, Maya; Giacomini, Kathleen M.

doi:10.1002/1520-6017(200104)90:4<397::aid-jps1000>3.0.co;2-d

Cited by 260 publications

(135 citation statements)

References 97 publications

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“…However, endogenous phosphorylation of S286 and S292 influences the binding sites for TPA ϩ and, to a lower extent, for quinine, but not that for TEA ϩ . These modulations of the substrate affinity of rOCT1 depending on phosphorylation of the molecule may explain the differences in apparent substrate affinities of OCTs determined in different organs or species or after expression of cloned transporters in different cellular systems (8,35).…”

Section: Discussionmentioning

confidence: 99%

Individual PKC-Phosphorylation Sites in Organic Cation Transporter 1 Determine Substrate Selectivity and Transport Regulation

Ciarimboli¹,

Koepsell²,

Iordanova³

et al. 2005

Journal of the American Society of Nephrology

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Section: Discussionmentioning

confidence: 99%

Individual PKC-Phosphorylation Sites in Organic Cation Transporter 1 Determine Substrate Selectivity and Transport Regulation

Ciarimboli¹,

Koepsell²,

Iordanova³

et al. 2005

Journal of the American Society of Nephrology

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“…We detected mRNA from OCT1 in 20 of 20 tumor samples from colon cancer patients and mRNA from OCT2 in 11 of 20 samples (11). There are three members of the human OCT family: hOCT1 is expressed primarily in the liver; hOCT2 in the kidney; and hOCT3 in the liver, heart, brain, and placenta (12). All are present in the intestinal/colorectal area to varying degrees (11,13).…”

mentioning

confidence: 99%

“…All are present in the intestinal/colorectal area to varying degrees (11,13). OCTs interact with organic substrates having M r Ͻ400 Da and overall positive charge (12). Oxaliplatin, a neutral compound, is therefore transported only after loss of the oxalate group to form mono-or dicationic species.…”

mentioning

confidence: 99%

cis -Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospects

Lovejoy

Todd

Zhang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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226

221

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We have identified unique chemical and biological properties of a cationic monofunctional platinum(II) complex, cis-diammine(pyridine)chloroplatinum(II), cis-[Pt(NH 3)2(py)Cl]؉ or cDPCP, a coordination compound previously identified to have significant anticancer activity in a mouse tumor model. This compound is an excellent substrate for organic cation transporters 1 and 2, also designated SLC22A1 and SLC22A2, respectively. These transporters are abundantly expressed in human colorectal cancers, where they mediate uptake of oxaliplatin, cis-[Pt(DACH)(oxalate)] (DACH ‫؍‬ trans-R,R-1,2-diaminocyclohexane), an FDA-approved first-line therapy for colorectal cancer. Unlike oxaliplatin, however, cDPCP binds DNA monofunctionally, as revealed by an x-ray crystal structure of cis-{Pt(NH 3)2(py)} 2؉ bound to the N7 atom of a single guanosine residue in a DNA dodecamer duplex. Although the quaternary structure resembles that of B-form DNA, there is a base-pair step to the 5 side of the Pt adduct with abnormally large shift and slide values, features characteristic of cisplatin intrastrand cross-links. cDPCP effectively blocks transcription from DNA templates carrying adducts of the complex, unlike DNA lesions of other monofunctional platinum(II) compounds like {Pt(dien)} 2؉ . cDPCP-DNA adducts are removed by the nucleotide excision repair apparatus, albeit much less efficiently than bifunctional platinum-DNA intrastrand cross-links. These exceptional characteristics indicate that cDPCP and related complexes merit consideration as therapeutic options for treating colorectal and other cancers bearing appropriate cation transporters.cancer therapy ͉ nucleotide excision repair ͉ organic cation transporter ͉ RNA polymerase II inhibition ͉ x-ray crystal structure

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“…Metformin serves as a substrate for organic ca tion transporters (OCTs), including OCT1 and OCT2, expressed in the liver and in the kidney, respectively (74,75). Organic cation transporter 1 (OCT1) is mainly responsible for metformin entry into enterocytes and hepatocytes.…”

Section: Organic Cation Transporters and Related Proteinsmentioning

confidence: 99%

The Role of Pharmacogenetics in the Treatment of Diabetes Mellitus / ULOGA FARMAKOGENETIKE U LEČNJU DIJABETES MELITUSA

Topić¹

2014

Journal of Medical Biochemistry

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Summary: Diabetes mellitus is a heterogeneous group of disorders in which particular disease phenotypes can be characterized by a specific etiology and/or pathogenesis of the disease, but in many cases its classification is greatly impeded due to significant phenotype overlapping. Diabetes is a wordwide epidemic with significant health and economic consequences. The frequency of type 2 diabetes (T2D) is much higher than type 1 diabetes (T1D). In adults, around 285 million people suffer from T2DM with a projected rise to 438 million in the next 20 years. A variety of pharmacological treatments exist for patients with T2D, in addition to dietary and physical activity. Pharmacologically, diabetes is treated with nine major classes of approved drugs, including insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs), meglitinides, a-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4) inhibitors. Treatment strategy for T2D is based mostly on oral hypoglycemic drug (OHD) efficacy assessed usually by HbA1c and/or fasting plasma glucose. The patients are often treated with more than one OHD in combination with the purpose to receive more effective treatment. Characterization of drug response is expected to substantially increase the ability to provide patients with the most effective treatment strategy. If pharmacogenetic testing for diabetes drugs could be used to predict treatment outcome, appropriate measures could be taken to treat T2D more efficiently. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs, the most used OHD. A comprehensive review of the pharmacogenetic studies of specific OHD is presented in this article. Understanding the pharmacogenetics of these drugs Kratak sadr`aj: Dijabetes melitus predstavlja heterogenu grupu pore me}aja u kojoj odre|eni fenotip mo`e karakterisati spe cifi~na etiologija i/ili patogeneza bolesti, ali u mnogim slu~ajevima njegova klasifikacija je vrlo ote`ana zbog zna~ajnog fenotipskog pre klapanja. Dijabetes je globalni epidemiolo{ki problem sa zna~ajnim zdravstvenim i ekonomskim posledicama. U~es talost tipa 2 dijabetesa (T2D) mno go je ve}a od tipa 1 dijabetesa. Kod odraslih, oko 285 miliona osoba boluje od T2D, s predvi|enim rastom do 438 miliona u slede}ih 20 godina. Za pacijente s dijabetesom tipa 2, uz ishranu i fizi~ku aktivnost, postoji niz farmakolo{kih lekova. Devet glavnih vrsta lekova odobreno je za le~enje T2D bolesnika: insulin i njegovi analozi, sulfonilureje, bi gvanidi, tiazolidindioni, meglitinidi, inhibitori a-glukozidaze, analozi amilina, mimetici inkretin hormona i inhibitori dipeptidil-peptidaze 4. Stra te gija le~enja T2D se temelji uglavnom na u~inkovitosti oralnih hipoglikemijskih lekova merenjem HbA1c i/ili glukoze nata{te. Bolesnici se ~esto le~e kombinacijom vi{e oralnih hipoglikemika kako bi se postigla {to uspe{ nija terapija. Ka ra kterizacija odgovora na lek obezbedi}e, kako se o~ekuje, mogu}nost uspe{nijeg leenja, odnosno...

show abstract

Transporters involved in the elimination of drugs in the kidney: Organic anion transporters and organic cation transporters

Cited by 260 publications

References 97 publications

Individual PKC-Phosphorylation Sites in Organic Cation Transporter 1 Determine Substrate Selectivity and Transport Regulation

Individual PKC-Phosphorylation Sites in Organic Cation Transporter 1 Determine Substrate Selectivity and Transport Regulation

cis -Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospects

The Role of Pharmacogenetics in the Treatment of Diabetes Mellitus / ULOGA FARMAKOGENETIKE U LEČNJU DIJABETES MELITUSA

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