ArticleDrug metabolism and disposition: the biological fate of chemicals2015
Atenolol Renal Secretion Is Mediated by Human Organic Cation Transporter 2 and Multidrug and Toxin Extrusion Proteins.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
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- Exploring Experimental and Statistical Approaches to Control Oversensitivity of In Vitro Permeability to Excipient Effects.Pharmaceutics · 2025Article
- Determination of metal ion transport rate of human ZIP4 using stable zinc isotopes.The Journal of biological chemistry · 2024Article
- Review
- Interaction and Transport of Benzalkonium Chlorides by the Organic Cation and Multidrug and Toxin Extrusion Transporters.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Use of a Double-Transfected System to Predict hOCT2/hMATE1-Mediated Renal Drug-Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Sweet Cherry Extract as Permeation Enhancer of Tyrosine Kinase Inhibitors: A Promising Prospective for Future Oral Anticancer Therapies.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Interlaboratory Variability in the Madin-Darby Canine Kidney Cell Proteome.Molecular pharmaceutics · 2023Article
- Kidney Drug Transporters in Pharmacotherapy.International journal of molecular sciences · 2023Review
- Quantitative Proteomics in Translational Absorption, Distribution, Metabolism, and Excretion and Precision Medicine.Pharmacological reviews · 2022Review
- Transport Turnover Rates for Human OCT2 and MATE1 Expressed in Chinese Hamster Ovary Cells.International journal of molecular sciences · 2022Article
- In Vitro Inhibition of Renal OCT2 and MATE1 Secretion by Antiemetic Drugs.International journal of molecular sciences · 2021Article
- Characterization ofMolecular pharmacology · 2020Article
- Genetically Engineered Human Kidney Cells for Real-Time Cytotoxicity Testing In Vitro.Molecular biotechnology · 2020Article
- Renal secretion of hydrochlorothiazide involves organic anion transporter 1/3, organic cation transporter 2, and multidrug and toxin extrusion protein 2-K.American journal of physiology. Renal physiology · 2019Article
- Intestinal Permeability and Drug Absorption: Predictive Experimental, Computational and In Vivo Approaches.Pharmaceutics · 2019Review
- Role of OCT1 in hepatocellular carcinoma.OncoTargets and therapy · 2019Article
- The Importance of Incorporating OCT2 Plasma Membrane Expression and Membrane Potential in IVIVE of Metformin Renal Secretory Clearance.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- Genetic Heterogeneity of SLC22 Family of Transporters in Drug Disposition.Journal of personalized medicine · 2018Review
- Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases.Journal of food and drug analysis · 2018Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Atenolol is a β-blocker widely used in the treatment of hypertension. Atenolol is cleared predominantly by the kidney by both glomerular filtration and active secretion, but the molecular mechanisms involved in its renal secretion are unclear. Using a panel of human embryonic kidney cell lines stably expressing human organic cation transporter (hOCT) 1-3, human organic anion transporter (hOAT) 1, hOAT3, human multidrug and toxin extrusion protein (hMATE) 1, and hMATE2-K, we found that atenolol interacted with both organic cation and anion transporters. However, it is transported by hOCT1, hOCT2, hMATE1, and hMATE2-K, but not by hOCT3, hOAT1, and hOAT3. A detailed kinetic analysis coupled with absolute quantification of membrane transporter proteins by liquid chromatography-tandem mass spectrometry revealed that atenolol is an excellent substrate for the renal transporters hOCT2, hMATE1, and hMATE2-K. The Km values for hOCT2, hMATE1, and hMATE2-K are 280 ± 4, 32 ± 5, and 76 ± 14 μM, respectively, and the calculated turnover numbers are 2.76, 0.41, and 2.20 s(-1), respectively. To demonstrate unidirectional transepithelial transport of atenolol, we developed and functionally validated a hOCT2/hMATE1 double-transfected Madin-Darby canine kidney cell culture model. Transwell studies showed that atenolol transport in the basal (B)-to-apical (A) direction is 27-fold higher than in the A-to-B direction, whereas its B-to-A/A-to-B transport ratio was only 2 in the vector-transfected control cells. The overall permeability of atenolol in the B-to-A direction in hOCT2/hMATE1 cells was 44-fold higher than in control cells. Together, our data support that atenolol tubular secretion is mediated through the hOCT2/hMATEs secretion pathway and suggest a significant role of organic cation transporters in the disposition of an important antihypertensive drug.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.