scholarly journals Atenolol Renal Secretion Is Mediated by Human Organic Cation Transporter 2 and Multidrug and Toxin Extrusion Proteins

2015 ◽  
Vol 43 (12) ◽  
pp. 1872-1881 ◽  
Author(s):  
Jia Yin ◽  
Haichuan Duan ◽  
Yoshiyuki Shirasaka ◽  
Bhagwat Prasad ◽  
Joanne Wang
Keyword(s):  
Organic Cation ◽  
Organic Cation Transporter ◽  
Renal Secretion ◽  
Organic Cation Transporter 2 ◽  
Toxin Extrusion

Tamsulosin Alters the Pharmacokinetics of Metformin Via Inhibition of Renal Multidrug and Toxin Extrusion Protein 1 and Organic Cation Transporter 2 in Rats

2021 ◽  
Author(s):  
Abdulaziz Ahmed A.Saad ◽  
Fan zhang ◽  
Moath Refata ◽  
Eyad Abdulwhab H.Mohammed ◽  
Mingkang Zhang ◽  
...  
Keyword(s):  
Organic Cation ◽  
Organic Cation Transporter ◽  
Organic Cation Transporter 2 ◽  
Toxin Extrusion

scholarly journals Renal secretion of hydrochlorothiazide involves organic anion transporter 1/3, organic cation transporter 2, and multidrug and toxin extrusion protein 2-K

2019 ◽  
Vol 317 (4) ◽  
pp. F805-F814
Author(s):  
Jia Yin ◽  
David J. Wagner ◽  
Bhagwat Prasad ◽  
Nina Isoherranen ◽  
Kenneth E. Thummel ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Organic Cation ◽  
Organic Anion ◽  
Organic Cation Transporter ◽  
Tubular Secretion ◽  
Organic Anion Transporter ◽  
Anion Transporters ◽  
Anion Transporter ◽  
Organic Cation Transporter 2 ◽  
Toxin Extrusion

Hydrochlorothiazide (HCTZ) is the most widely used thiazide diuretic for the treatment of hypertension either alone or in combination with other antihypertensives. HCTZ is mainly cleared by the kidney via tubular secretion, but the underlying molecular mechanisms are unclear. Using cells stably expressing major renal organic anion and cation transporters [human organic anion transporter 1 (hOAT1), human organic anion transporter 3 (hOAT3), human organic cation transporter 2 (hOCT2), human multidrug and toxin extrusion 1 (hMATE1), and human multidrug and toxin extrusion 2-K (hMATE2-K)], we found that HCTZ interacted with both organic cation and anion transporters. Uptake experiments further showed that HCTZ is transported by hOAT1, hOAT3, hOCT2, and hMATE2-K but not by hMATE1. Detailed kinetic analysis coupled with quantification of membrane transporter proteins by targeted proteomics revealed that HCTZ is an excellent substrate for hOAT1 and hOAT3. The apparent affinities ( Km) for hOAT1 and hOAT3 were 112 ± 8 and 134 ± 13 μM, respectively, and the calculated turnover numbers ( kcat) were 2.48 and 0.79 s−1, respectively. On the other hand, hOCT2 and hMATE2-K showed much lower affinity for HCTZ. The calculated transport efficiency ( kcat/ Km) at the single transporter level followed the rank order of hOAT1> hOAT3 > hOCT2 and hMATE2-K, suggesting a major role of organic anion transporters in tubular secretion of HCTZ. In vitro inhibition experiments further suggested that HCTZ is not a clinically relevant inhibitor for hOAT1 or hOAT3. However, strong in vivo inhibitors of hOAT1/3 may alter renal secretion of HCTZ. Together, our study elucidated the molecular mechanisms underlying renal handling of HCTZ and revealed potential pathways involved in the disposition and drug-drug interactions for this important antihypertensive drug in the kidney.

Effects of genetic variants in SLC22A2 organic cation transporter 2 and SLC47A1 multidrug and toxin extrusion 1 transporter on cisplatin-induced adverse events

2012 ◽  
Vol 16 (6) ◽  
pp. 843-851 ◽  
Author(s):  
Kazufumi Iwata ◽  
Keiji Aizawa ◽  
Saori Kamitsu ◽  
Sachiko Jingami ◽  
Eiko Fukunaga ◽  
...  
Keyword(s):  
Adverse Events ◽  
Genetic Variants ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Organic Cation Transporter 2 ◽  
Toxin Extrusion

Renal vectorial transport of berberine mediated by organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins 1 (MATE1) in rats

2017 ◽  
Vol 39 (1) ◽  
pp. 47-58 ◽  
Author(s):  
Rong Shi ◽  
Yuanyuan Yang ◽  
Zhangyao Xu ◽  
Yan Dai ◽  
Min Zheng ◽  
...  
Keyword(s):  
Organic Cation ◽  
Organic Cation Transporter ◽  
Organic Cation Transporter 2 ◽  
Vectorial Transport ◽  
Toxin Extrusion

scholarly journals In Vitro Inhibition of Renal OCT2 and MATE1 Secretion by Antiemetic Drugs

2021 ◽  
Vol 22 (12) ◽  
pp. 6439
Author(s):  
Blessy George ◽  
Xia Wen ◽  
Edgar A. Jaimes ◽  
Melanie S. Joy ◽  
Lauren M. Aleksunes
Keyword(s):  
Organic Cation ◽  
Mdck Cells ◽  
Organic Cation Transporter ◽  
Hek293 Cells ◽  
Intracellular Accumulation ◽  
Renal Secretion ◽  
Transcellular Transport ◽  
Antiemetic Drugs ◽  
Organic Cation Transporter 2

The organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) mediate the renal secretion of drugs. Recent studies suggest that ondansetron, a 5-HT3 antagonist drug used to prevent nausea and vomiting, can inhibit OCT2- and MATE1-mediated transport. The purpose of this study was to test the ability of five 5-HT3 antagonist drugs to inhibit the OCT2 and MATE1 transporters. The transport of the OCT2/MATE1 probe substrate ASP+ was assessed using two models: (1) HEK293 kidney cells overexpressing human OCT2 or MATE1, and (2) MDCK cells transfected with human OCT2 and MATE1. In HEK293 cells, the inhibition of ASP+ uptake by OCT2 listed in order of potency was palonosetron (IC50: 2.6 μM) > ondansetron > granisetron > tropisetron > dolasetron (IC50: 85.4 μM) and the inhibition of ASP+ uptake by MATE1 in order of potency was ondansetron (IC50: 0.1 μM) > palonosetron = tropisetron > granisetron > dolasetron (IC50: 27.4 μM). Ondansetron (0.5–20 μM) inhibited the basolateral-to-apical transcellular transport of ASP+ up to 64%. Higher concentrations (10 and 20 μM) of palonosetron, tropisetron, and dolasetron similarly reduced the transcellular transport of ASP+. In double-transfected OCT2-MATE1 MDCK cells, ondansetron at concentrations of 0.5 and 2.5 μM caused significant intracellular accumulation of ASP+. Taken together, these data suggest that 5-HT3 antagonist drugs may inhibit the renal secretion of cationic drugs by interfering with OCT2 and/or MATE1 function.

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