Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter

Gründemann, Dirk; Schechinger, Birgit; Rappold, Gudrun; Schömig, Edgar

doi:10.1038/1557

Cited by 374Neuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on BehaviorReceptor Mechanisms and Signaling

Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter

Gründemann, Dirk, Schechinger, Birgit, Rappold, Gudrun, Schömig, Edgar·1998·Nature Neuroscience

DOI 10.1038/1557

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Catecholamine levels are further increased by glucocorticoids, which block the transporters on glia that normally remove catecholamines from the extracellular space.
“Catecholamine levels are further increased by glucocorticoids, which block the transporters on glia that normally remove catecholamines from the extracellular space51.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [51]

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“Recent evidence indicates that OCT3 is identical with the extraneuronal monoamine transporter (uptake2) that has been described functionally as a Na1-and Cl2-independent transport system for monoamines (Grundemann et al., 1998; Wu et al., 1998a).”
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Neurotransmitter transporters: fruitful targets for CNS drug discovery
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“…and neurotransmitter systems thought to be involved in the mediation of PTSD symptoms (Sapolsky, 1985, 1986; McEwen, 2000; Schulkin et al, 1998; Grundemann et al, 1998; Lupien et al, 1998, 1999; Newcomer et al, Online publication: 13 February 2004 at http://www.acnp.org/citations/…”
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TISSUE DISTRIBUTION AND ONTOGENY OF ORGANIC CATION TRANSPORTERS IN MICE
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“Oct3 is also called extraneuronal monoamine transporter for its role in the extraneuronal monoamine uptake system (uptake2) (Grundemann et al., 1998; Wu et al., 1998a).”
Background
Corticosterone Acts in the Nucleus Accumbens to Enhance Dopamine Signaling and Potentiate Reinstatement of Cocaine Seeking
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“PMAT is the least sensitive to corticosterone (Ki 450 M), followed by OCT1 (IC50 150 M), OCT2 (IC50 5 M), and OCT3 (IC50 0.04 – 0.2 M) (Grundemann et al., 1998b; Shang et al., 2003; Gorboulev et al., 2005; Schomig et al., 2006; Duan and Wang, 2010).”
BackgroundInfluential
G Protein-Coupled Receptors in and on the Cell Nucleus: A New Signaling Paradigm?
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“For example, nonselective catecholamine uptake systems such as extraneuronal monoamine transporter (EMT or OCT3) are found in several tissues [(69,70); reviewed in Ref.”
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Expression and immunolocalization of the plasma membrane monoamine transporter in the brain
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“Human OCT3 favors epinephrine and NE over 5-HT and DA (Grundemann et al., 1998; Amphoux et al., 2006), and is broadly expressed in a number of tissues, including the liver, heart, placenta, skeletal muscle, kidney, and brain (Grundemann et al.”
BackgroundInfluential
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“Organic cation transporter 3 (OCT3) was first cloned from rat placenta (Kekuda et al., 1998), and its orthologues were also cloned from humans and mice (Grü ndemann et al., 1998; Verhaagh et al., 1999).”
BackgroundInfluential
Epithelial Organic Cation Transporters Ensure pH-Dependent Drug Absorption in the Airway
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“Five human organic cation transporters have been cloned to date: the potential dependent organic cation transporters OCT1 (6), OCT2 (7), and OCT3 (8), and the pH-dependent organic cation/carnitine transporters OCTN1 (9) and OCTN2 (10).”
BackgroundInfluential
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Self-citation
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“cloned as the extraneuronal monoamine transporter by different groups [46,47].”
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Organic cation transporters and their pharmacokinetic and pharmacodynamic consequences.
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“These properties have led to the suggestion that OCT3 may act as a “second line of defense,” contributing to the clearance of extracellular monoamines that escape the high-affinity presynaptic transporters (Grundemann et al., 1998).”
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Vialou, V., Balasse, L., Callebert, J., Launay, J., Giros, B., & Gautron, S. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05506.x · Cited by 114 · see citing works
“Rat and human OCT3 were shown to be able to transport all aminergic neurotransmitters in cellular expression systems (Grundemann et al. 1998b, 1999; Kekuda et al. 1998; Wu et al. 1998).”
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Regulation of organic cation transport
Ciarimboli, G., & Schlatter, E. (2005) · Pflügers Archiv · doi:10.1007/s00424-004-1355-5 · Cited by 114 · see citing works
“Three isoforms of OCTs have been identified in rat, mouse and man: OCT1 [23, 24], OCT2 [24, 25, 26] and OCT3 [27, 28, 29].”
Background
Norepinephrine transporter (NET), serotonin transporter (SERT), vesicular monoamine transporter (VMAT2) and organic cation transporters (OCT1, 2 and EMT) in human placenta from pre-eclamptic and normotensive pregnancies.
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“NM_021977 [24].”
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Nucleoside transporter proteins as biomarkers of drug responsiveness and drug targets
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“…the family, there are several subfamilies, which consist of members that cluster together based on sequence homology, including the OATs, the OCTs, and the OCTNs. hOCT1, hOCT2, and hOCT3 are encoded by genes SLC22A1-3 (Koehler et al., 1997; Grundemann et al., 1998; Grundemann and Schomig, 2000).”
Background
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Self-citation
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Schmitt, A., Mössner, R., Gossmann, A., Fischer, I., Gorboulev, V., Murphy, D., Koepsell, H., & Lesch, K. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10521 · Cited by 106 · see citing works
“For both EMT and rOCT3, a broad substrate specifity was described (Gründemann et al., 1998; Wu et al., 1998; Kekuda et al., 1998; Rajan et al., 2000).”
BackgroundInfluential
Subtype-Specific Affinity for Corticosterone of Rat Organic Cation Transporters rOCT1 and rOCT2 Depends on Three Amino Acids within the Substrate Binding Region
Gorboulev, V., Shatskaya, N., Volk, C., & Koepsell, H. (2005) · Molecular Pharmacology · doi:10.1124/mol.104.008821 · Cited by 105 · see citing works
“Like other OCTs, hOCT3 translocates monoamine neurotransmitters.”
Influential
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Pietig, G., Mehrens, T., Hirsch, J., Çetinkaya, I., Piechota, H., & Schlatter, E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104617200 · Cited by 104
Working memory-related frontal theta activity is decreased under acute stress
Gärtner, M., Rohde-Liebenau, L., Grimm, S., & Bajbouj, M. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.02.009 · Cited by 103 · see citing works
“Furthermore, it is assumed that the impairing effect of high Ca and Gc concentrations is mutually reinforced (Grundemann et al., 1998).”
Background
Molecular mechanism of histamine clearance by primary human astrocytes
Yoshikawa, T., Naganuma, F., Iida, T., Nakamura, T., Harada, R., Mohsen, A. S., Kasajima, A., Sasano, H., & Yanai, K. (2013) · Glia · doi:10.1002/glia.22484 · Cited by 106 · see citing works
“OCT2 was not detected in primary human astrocytes, but OCT3 and PMAT were expressed (Fig.”
BackgroundInfluential
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Regulation of human organic cation transporter hOCT2 by PKA, PI3K, and calmodulin-dependent kinases.
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“In 1997, the first human organic cation transporters were cloned (5, 7, 35, 43, 47).”
Background
Extraneuronal monoamine transporter and organic cation transporters 1 and 2: a review of transport efficiency.
Schömig, E., Lazar, A., & Gründemann, D. (2006) · Handbook of Experimental Pharmacology · doi:10.1007/3-540-29784-7_8 · Cited by 97 · see citing works
Self-citation
Comparison of Inhaled Fluticasone with Intravenous Hydrocortisone in the Treatment of Adult Acute Asthma
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Corticosterone time-dependently modulates β-adrenergic effects on long-term potentiation in the hippocampal dentate gyrusPreprint
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Astroglial dopamine transport is mediated by norepinephrine transporter
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Molecular and functional characterization of an Na+‐independent choline transporter in rat astrocytes
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“Furthermore, in this study, RT-PCR data show that mRNA for OCT1, OCT2 and OCT3 was expressed at very low levels in rat astrocytes.”
BackgroundInfluential
Corticosterone modulates noradrenaline‐induced melatonin synthesis through inhibition of nuclear factor kappa B
Ferreira, Z., Fernandes, P., Duma, D., Assreuy, J., Avellar, M. C. W., & Markus, R. (2005) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2004.00191.x · Cited by 92 · see citing works
“This uptake has a higher affinity for adrenaline, when compared with noradrenaline [13], and is blocked by corticosterone through a direct, nongenomic mechanism [15].”
Background

Authors: Gründemann, D., Schechinger, B., Rappold, G., & Schömig, E.
Affiliations: Heidelberg University (DE)
Corresponding author: Gründemann, Dirk
ORCID: Gründemann, Dirk
Rappold, Gudrun
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 1998-09
Volume: 1
Issue: 5
Pages: 349-351
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/1557
OpenAlex: W1493374490
Cited by: 374
References: 0
Citations by year: 2026: 2 · 2025: 2 · 2024: 4 · 2023: 10 · 2022: 13 · 2021: 13 · 2020: 9 · 2019: 11 · 2018: 9 · 2017: 8 · 2016: 16 · 2015: 13 · 2014: 17 · 2013: 25 · 2012: 13
FWCI: 5.15
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords: sympathetic innervation, pharmacological characterization
MeSH terms: Organic Cation Transporter 3, Amino Acid Sequence, Animals, Carrier Proteins, Cell Line, Chromosome Mapping, Chromosomes, Human, Pair 6, Corticosterone, Humans, Kinetics, Molecular Sequence Data, Myocardium, Norepinephrine, 1-Methyl-4-phenylpyridinium, Organic Cation Transport Proteins, Rats

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Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter

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