ArticleMolecular and cellular biology2001
Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (Oct1 [Slc22a1]) gene.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 224 citations in OpenAlex.
- Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics.Clinical pharmacology and therapeutics · 2008Trial
- 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
- High Throughput Screening of a Prescription Drug Library for Inhibitors of Organic Cation Transporter 3, OCT3.Pharmaceutical research · 2022Article
- Review
- Article
- Solute Carrier Transportome in Chemotherapy-Induced Adverse Drug Reactions.Reviews of physiology, biochemistry and pharmacology · 2022Article
- Functional and Biochemical Consequences of Disease Variants in Neurotransmitter Transporters: A Special Emphasis on Folding and Trafficking Deficits.Pharmacology & therapeutics · 2021Review
- Comparison of Hepatic Transporter Tissue Expression in Rodents and Interspecies Hepatic OCT1 Activity.The AAPS journal · 2021Article
- Organic Cation Transporters in Psychiatric Disorders.Handbook of experimental pharmacology · 2021Article
- Organic Cation Transporter 1 an Intestinal Uptake Transporter: Fact or Fiction?Frontiers in pharmacology · 2021Review
- Influence of YES1 Kinase and Tyrosine Phosphorylation on the Activity of OCT1.Frontiers in pharmacology · 2021Article
- Influence of Cation Transporters (OCTs and MATEs) on the Renal and Hepatobiliary Disposition of [Pharmaceutical research · 2021Article
- Trospium Chloride Transport by Mouse Drug Carriers of the Slc22 and Slc47 Families.International journal of molecular sciences · 2020Article
- Using Ex Vivo Porcine Jejunum to Identify Membrane Transporter Substrates: A Screening Tool for Early-Stage Drug Development.Biomedicines · 2020Article
- Characterization ofMolecular pharmacology · 2020Article
- An Interspecies Molecular and Functional Study of Organic Cation Transporters at the Blood-Brain Barrier: From Rodents to Humans.Pharmaceutics · 2020Article
- Pharmacokinetics of Organic Cation Transporter 1 (OCT1) Substrates in Oct1/2 Knockout Mice and Species Difference in Hepatic OCT1-Mediated Uptake.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Enantioselective Drug Recognition by Drug Transporters.Molecules (Basel, Switzerland) · 2018Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The polyspecific organic cation transporter 1 (OCT1 [SLC22A1]) mediates facilitated transport of small (hydrophilic) organic cations. OCT1 is localized at the basolateral membrane of epithelial cells in the liver, kidney, and intestine and could therefore be involved in the elimination of endogenous amines and xenobiotics via these organs. To investigate the pharmacologic and physiologic role of this transport protein, we generated Oct1 knockout (Oct1(-/-)) mice. Oct1(-/-) mice appeared to be viable, healthy, and fertile and displayed no obvious phenotypic abnormalities. The role of Oct1 in the pharmacology of substrate drugs was studied by comparing the distribution and excretion of the model substrate tetraethylammonium (TEA) after intravenous administration to wild-type and Oct1(-/-) mice. In Oct1(-/-) mice, accumulation of TEA in liver was four to sixfold lower than in wild-type mice, whereas direct intestinal excretion of TEA was reduced about twofold. Excretion of TEA into urine over 1 h was 53% of the dose in wild-type mice, compared to 80% in knockout mice, probably because in Oct1(-/-) mice less TEA accumulates in the liver and thus more is available for rapid excretion by the kidney. In addition, we found that absence of Oct1 leads to decreased liver accumulation of the anticancer drug metaiodobenzylguanidine and the neurotoxin 1-methyl-4-phenylpyridium. In conclusion, our data show that Oct1 plays an important role in the uptake of organic cations into the liver and in their direct excretion into the lumen of the small intestine.
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