English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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.

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