ArticlePflugers Archiv : European journal of physiology2014
The organic cation transporter 3 (OCT3) as molecular target of psychotropic drugs: transport characteristics and acute regulation of cloned murine OCT3.
Article in Pflugers Archiv : European journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
- Guilty by association: direct interaction with the tetraspanin CD63 suggests a role for organic cation transporter 3 in histamine release from granulocytes.Journal of biomedical science · 2025Article
- Modulation of Multispecific Transporters byPharmaceutics · 2024Article
- Organic cation transporters in psychiatric and substance use disorders.Pharmacology & therapeutics · 2024Review
- Role of Mouse Organic Cation Transporter 2 for Nephro- and Peripheral Neurotoxicity Induced by Chemotherapeutic Treatment with Cisplatin.International journal of molecular sciences · 2023Article
- Chronic administration of glucocorticoid receptor ligands increases anxiety-like behavior and selectively increase serotonin transporters in the ventral hippocampus.Brain research · 2023Article
- Interaction of Masitinib with Organic Cation Transporters.International journal of molecular sciences · 2022Article
- MPPInternational journal of molecular sciences · 2022Article
- Analysis of OCT1, OCT2 and OCT3 gene polymorphisms among Type 2 diabetes mellitus subjects in Indian ethnicity, Malaysia.Saudi journal of biological sciences · 2022Article
- Interaction Profiles of Central Nervous System Active Drugs at Human Organic Cation Transporters 1-3 and Human Plasma Membrane Monoamine Transporter.International journal of molecular sciences · 2021Article
- Uptake of Biotinylated Spermine in Astrocytes: Effect of Cx43 siRNA, HIV-Tat Protein and Polyamine Transport Inhibitor on Polyamine Uptake.Biomolecules · 2021Article
- Substrates and Inhibitors of Organic Cation Transporters (OCTs) and Plasma Membrane Monoamine Transporter (PMAT) and Therapeutic Implications.Handbook of experimental pharmacology · 2021Article
- The Interaction of Organic Cation Transporters 1-3 and PMAT with Psychoactive Substances.Handbook of experimental pharmacology · 2021Review
- Organic Cation Transporters in Psychiatric Disorders.Handbook of experimental pharmacology · 2021Article
- Rapid Regulation of Human Multidrug and Extrusion Transporters hMATE1 and hMATE2K.International journal of molecular sciences · 2020Article
- Regulation Mechanisms of Expression and Function of Organic Cation Transporter 1.Frontiers in pharmacology · 2020Review
- Effects of Single Nucleotide Polymorphism Ala270Ser (rs316019) on the Function and Regulation of hOCT2.Biomolecules · 2019Article
- Comparative analysis of novel decynium-22 analogs to inhibit transport by the low-affinity, high-capacity monoamine transporters, organic cation transporters 2 and 3, and plasma membrane monoamine transporter.European journal of pharmacology · 2019Article
- The pharmacokinetics of ketamine following intramuscular injection to F344 rats.Drug testing and analysis · 2019Article
- Organic cation transporter 3 mediates cisplatin and copper cross-resistance in hepatoma cells.Oncotarget · 2018Article
- What do drug transporters really do?Nature reviews. Drug discovery · 2015Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The organic cation transporter 3 (OCT3) is a widely expressed transporter for endogenous and exogenous organic cations. Of particular interest is OCT3 expression and function in the brain, where it plays a role in serotonin clearance and influences mood and behavior. Protein kinase signaling mediates rapid modulation of cerebral processes, but little is known about acute regulation of OCT3 by protein kinases. Therefore, we cloned mouse OCT3 (mOCT3) and generated a human embryonic kidney cell line stably expressing the transporter to study transport characteristics, acute regulation by protein kinases, and interaction with psychotropic drugs. Uptake measurement was performed using the fluorescent cation 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP(+), 1 μM) as a substrate. The translational value of these findings was determined by comparing results obtained with cloned mouse and human OCT3. mOCT3-mediated transport is membrane potential dependent and pH independent. ASP(+) uptake by mOCT3 and human OCT3 (hOCT3) was efficiently inhibited by 1-methyl-4-phenylpyridinium, tetrapentylammonium (TPA(+)), corticosterone, serotonin, and histamine and by the drugs ketamine, fluoxetine, and diazepam. The half maximal inhibitory concentrations of mOCT3 and hOCT3 for TPA(+), serotonin, diazepam, and ketamine are significantly different. Diazepam is a non-transported inhibitor. Furthermore, the activities of mOCT3 and hOCT3 are acutely regulated by the p56 (lck) tyrosine kinase by decreasing their V max. Studies with freshly isolated renal proximal tubules from mOCT1/2(-/-) mice, in which mOCT3 is the only OCT present, confirmed this regulation pathway. Only the activity of hOCT3 is regulated by calmodulin. These findings suggest that even though many transport properties of mOCT3 and hOCT3 are similar, there are also species-specific aspects of OCT3 function.
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