ArticleMolecular and cellular biology2003
Deficiency in the organic cation transporters 1 and 2 (Oct1/Oct2 [Slc22a1/Slc22a2]) in mice abolishes renal secretion of organic cations.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 261 citations in OpenAlex.
- Pooled it
- Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans.Clinical pharmacology and therapeutics · 2025Trial
- Polymorphisms of SLCO1B1 rs4149056 and SLC22A1 rs2282143 are associated with responsiveness to acitretin in psoriasis patients.Scientific reports · 2018Trial
- The Molecular Mechanisms of Metformin's Action on Blood Lipid Profile in Diabetic Patients.International journal of molecular sciences · 2026Review
- Development and Validation of a UPLC-MS/MS Method for the Quantification of Amantadine in Rat Plasma: Application to a Pharmacokinetic Study Under High-Altitude Hypoxia and Mechanistic Insights.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Exploring the Therapeutic Role of Pregnane X Receptor Activation in Acute Kidney Injury: Mechanisms and Clinical Implications.Current molecular medicine · 2026Review
- Applying molecular dynamics simulations to validate OCT1 substrates uncovers vitamin K1 as a high-affinity ligand.Frontiers in pharmacology · 2026Article
- Predicting OCT2/MATEs-Mediated Drug Interactions in Healthy Volunteers and Patients with Chronic Kidney Disease: Insights from Extended Clearance Concept, Endogenous Biomarkers, and In Vitro Inhibition Studies (Perspectives from the International Transporter Consortium).Clinical pharmacology and therapeutics · 2025Review
- Role of Transport Proteins for the Renal Handling of L-Arginine and Related Derivatives.International journal of molecular sciences · 2025Review
- Transport of Small Aliphatic Amines by Polyspecific Solute Carriers: Deciphering Structure-Function Relationships.ACS pharmacology & translational science · 2025Article
- Substrate-specific inhibition of organic cation transporter 1 revealed using a multisubstrate drug cocktail.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants.Science (New York, N.Y.) · 2025Article
- Article
- Organic cation transporters in psychiatric and substance use disorders.Pharmacology & therapeutics · 2024Review
- Summarizing studies using constitutive genetic deficiency to investigate behavioural influences of uptake 2 monoamine transporters.Basic & clinical pharmacology & toxicology · 2023Review
- Organic cation transporter 2 contributes to SSRI antidepressant efficacy by controlling tryptophan availability in the brain.Translational psychiatry · 2023Article
- The Impacts of Slc19a3 Deletion and Intestinal SLC19A3 Insertion on Thiamine Distribution and Brain Metabolism in the Mouse.Metabolites · 2023Article
- Role of Mouse Organic Cation Transporter 2 for Nephro- and Peripheral Neurotoxicity Induced by Chemotherapeutic Treatment with Cisplatin.International journal of molecular sciences · 2023Article
- Investigations with Drugs and Pesticides Revealed New Species- and Substrate-Dependent Inhibition by Elacridar and Imazalil inInternational journal of molecular sciences · 2022Article
- Epigenomic and transcriptomic analyses define core cell types, genes and targetable mechanisms for kidney disease.Nature genetics · 2022Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The polyspecific organic cation transporters 1 and 2 (Oct1 and -2) transport a broad range of substrates, including drugs, toxins, and endogenous compounds. Their strategic localization in the basolateral membrane of epithelial cells in the liver, intestine (Oct1), and kidney (Oct1 and Oct2) suggests that they play an essential role in removing noxious compounds from the body. We previously showed that in Oct1(-/-) mice, the hepatic uptake and intestinal excretion of organic cations are greatly reduced. Since Oct1 and Oct2 have extensively overlapping substrate specificities, they might be functionally redundant. To investigate the pharmacologic and physiologic roles of these proteins, we generated Oct2 single-knockout and Oct1/2 double-knockout mice. Oct2(-/-) and Oct1/2(-/-) mice are viable and fertile and display no obvious phenotypic abnormalities. Absence of Oct2 in itself had little effect on the pharmacokinetics of tetraethylammonium (TEA), but in Oct1/2(-/-) mice, renal secretion of this compound was completely abolished, leaving only glomerular filtration as a TEA clearance mechanism. As a consequence, levels of TEA were substantially increased in the plasma of Oct1/2(-/-) mice. This study shows that Oct1 and Oct2 together are essential for renal secretion of (small) organic cations. A deficiency in these proteins may thus result in increased drug sensitivity and toxicity.
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Registered trials
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.