ArticleMolecular and cellular biology2001
Impaired activity of the extraneuronal monoamine transporter system known as uptake-2 in Orct3/Slc22a3-deficient mice.
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 82 papers.
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82 citing papers in PubMed, 202 citations in OpenAlex.
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- Serotonin Transporter-dependent Histone Serotonylation in Placenta Contributes to the Neurodevelopmental Transcriptome.Journal of molecular biology · 2024Article
- Organic cation transporters in psychiatric and substance use disorders.Pharmacology & therapeutics · 2024Review
- Cardiac contraction and relaxation are regulated by distinct subcellular cAMP pools.Nature chemical biology · 2024Article
- Serotonin transporter-dependent histone serotonylation in placenta contributes to the neurodevelopmental transcriptome.bioRxiv : the preprint server for biology · 2023Article
- Determination and disposition of meta-iodobenzylguanidine in plasma and heart of transporter-deficient mice by UPLC-MS/MS.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2023Article
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- Role of OCT3 and DRP1 in the Transport of Paraquat in Astrocytes: A Mouse Study.Environmental health perspectives · 2022Article
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- Solute Carrier Transportome in Chemotherapy-Induced Adverse Drug Reactions.Reviews of physiology, biochemistry and pharmacology · 2022Article
- Role of Organic Cation Transporter 3 and Plasma Membrane Monoamine Transporter in the Rewarding Properties and Locomotor Sensitizing Effects of Amphetamine in Male andFemale Mice.International journal of molecular sciences · 2021Article
- Overlap and Specificity in the Substrate Spectra of Human Monoamine Transporters and Organic Cation Transporters 1, 2, and 3.International journal of molecular sciences · 2021Article
- Functional and Biochemical Consequences of Disease Variants in Neurotransmitter Transporters: A Special Emphasis on Folding and Trafficking Deficits.Pharmacology & therapeutics · 2021Review
- Functional inhibition of Oct leads to HNF4α upregulation.Experimental and therapeutic medicine · 2021Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two uptake systems that control the extracellular concentrations of released monoamine neurotransmitters such as noradrenaline and adrenaline have been described. Uptake-1 is present at presynaptic nerve endings, whereas uptake-2 is extraneuronal and has been identified in myocardium and vascular and nonvascular smooth muscle cells. The gene encoding the uptake-2 transporter has recently been identified in humans (EMT), rats (OCT3), and mice (Orct3/Slc22a3). To generate an in vivo model for uptake-2, we have inactivated the mouse Orct3 gene. Homozygous mutant mice are viable and fertile with no obvious physiological defect and also show no significant imbalance of noradrenaline or dopamine. However, Orct3-null mice show an impaired uptake-2 activity as measured by accumulation of intravenously administered [(3)H]MPP(+) (1-methyl-4-phenylpyridinium). A 72% reduction in MPP(+) levels was measured in hearts of both male and female Orct3 mutant mice. No significant differences between wild-type and mutant mice were found in any other adult organ or in plasma. When [(3)H]MPP(+) was injected into pregnant females, a threefold-reduced MPP(+) accumulation was observed in homozygous mutant embryos but not in their placentas or amniotic fluid. These data show that Orct3 is the principal component for uptake-2 function in the adult heart and identify the placenta as a novel site of action of uptake-2 that acts at the fetoplacental interface.
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