Evidence map›Paper›PMID 31912366›Full record

ArticleNeurochemical research2020

Amphetamine Stimulates Endocytosis of the Norepinephrine and Neuronal Glutamate Transporters in Cultured Locus Coeruleus Neurons.

Suzanne M Underhill, Mark S Colt, Susan G Amara

Open access · hybridAbstract read
In one paragraph

Article in Neurochemical research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.1field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Psychostimulants and social behaviors.Frontiers in pharmacology · 2024
    Review
  7. Article
  8. Frontiers in psychiatry · 2023
    Article
  9. Article
  10. Article
  11. Substance abuse and neurotransmission.Advances in pharmacology (San Diego, Calif.) · 2022
    Article
  12. Trace amine-associated receptor 1 and drug abuse.Advances in pharmacology (San Diego, Calif.) · 2022
    Article
  13. Review
  14. Review
  15. Review
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Suzanne M UnderhillLaboratory of Molecular and Cellular Neurobiology, National Institute of Mental Health, National Institutes of Health, 35 Convent Drive, Room 3A:209, Bethesda, MD, 20892, USA. Suzanne.Underhill@nih.gov.
Mark S ColtLaboratory of Molecular and Cellular Neurobiology, National Institute of Mental Health, National Institutes of Health, 35 Convent Drive, Room 3A:209, Bethesda, MD, 20892, USA.
Susan G AmaraLaboratory of Molecular and Cellular Neurobiology, National Institute of Mental Health, National Institutes of Health, 35 Convent Drive, Room 3A:209, Bethesda, MD, 20892, USA.
National Institute of Mental Health · US

Funding

Structure, Function and Pharmacology of Neurotransmitter Reuptake SystemsZIAMH002946 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI AMARA, SUSAN · 2013 to 2025
$26.6M
Division of Intramural Research, National Institute of Allergy and Infectious Diseases (US) ZIAMH002946Intramural NIH HHS ZIA MH002946
6 · The paper itself

Abstract

Amphetamines and amphetamine-derivatives elevate neurotransmitter concentrations by competing with endogenous biogenic amines for reuptake. In addition, AMPHs have been shown to activate endocytosis of the dopamine transporter (DAT) which further elevates extracellular dopamine (DA). We previously found that the biochemical cascade leading to this cellular process involves entry of AMPH into the cell through the DAT, stimulation of an intracellular trace amine-associated receptor, TAAR1, and activation of the small GTPase, RhoA. We also showed that the neuronal glutamate transporter, EAAT3, undergoes endocytosis via the same cascade in DA neurons, leading to potentiation of glutamatergic inputs. Since AMPH is a transported inhibitor of both DAT and the norepinephrine transporter (NET), and EAAT3 is also expressed in norepinephrine (NE) neurons, we explored the possibility that this signaling cascade occurs in NE neurons. We found that AMPH can cause endocytosis of NET as well as EAAT3 in NE neurons. NET endocytosis is dependent on TAAR1, RhoA, intracellular calcium and CaMKII activation, similar to DAT. However, EAAT3 endocytosis is similar in all regards except its dependence upon CaMKII activation. RhoA activation is dependent on calcium, but not CaMKII, explaining a divergence in AMPH-mediated endocytosis of DAT and NET from that of EAAT3. These data indicate that AMPHs and other TAAR1 agonists can affect glutamate signaling through internalization of EAAT3 in NE as well as DA neurons.

Indexed as

Adrenergic Uptake InhibitorsAmino Acid Transport System X-AGAmphetamineAnimalsDopaminergic NeuronsDopamine Uptake InhibitorsEndocytosisExcitatory Amino Acid Transporter 3HEK293 CellsHumansLocus CoeruleusMiceNorepinephrine Plasma Membrane Transport ProteinsAdrenergic Uptake InhibitorsAmino Acid Transport System X-AGAmphetamineDopamine Uptake InhibitorsExcitatory Amino Acid Transporter 3Norepinephrine Plasma Membrane Transport ProteinsSLC1A1 protein, humanEAAT3Locus coeruleusNETNorepinephrineRhoATAAR1

Identifiers

PMID31912366
PMCPMC7260265
OpenAlexW2999145988

What OpenQuestion holds

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Registered trials

None linked

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.