Role of the Intracellular Nucleoside Transporter ENT3 in Transmitter and High K Stimulation of Astrocytic ATP Release Investigated Using siRNA Against ENT3
This study investigates the role of the intracellular adenosine transporter equilibrative nucleoside transporter 3 (ENT3) in stimulated release of the gliotransmitter adenosine triphosphate (ATP) from astrocytes. Within the past 20 years, our understanding of the importance of astrocytic handling of...
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doaj-6361bf33301d41efb7b741cf6c6cf7dd2020-11-25T03:18:22ZengSAGE PublishingASN Neuro1759-09142014-07-01610.1177/175909141454343910.1177_1759091414543439Role of the Intracellular Nucleoside Transporter ENT3 in Transmitter and High K Stimulation of Astrocytic ATP Release Investigated Using siRNA Against ENT3Dan Song0Junnan Xu1Qiufang Bai2Liping Cai3Leif Hertz4Liang Peng5 Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, P. R. China Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, P. R. China Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, P. R. China Laboratory of Molecular Biology, Liaoning University of Traditional Chinese Medicine, Shenyang, P. R. China Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, P. R. China Laboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Shenyang, P. R. ChinaThis study investigates the role of the intracellular adenosine transporter equilibrative nucleoside transporter 3 (ENT3) in stimulated release of the gliotransmitter adenosine triphosphate (ATP) from astrocytes. Within the past 20 years, our understanding of the importance of astrocytic handling of adenosine, its phosphorylation to ATP, and release of astrocytic ATP as an important transmitter has become greatly expanded. A recent demonstration that the mainly intracellular nucleoside transporter ENT3 shows much higher expression in freshly isolated astrocytes than in a corresponding neuronal preparation leads to the suggestion that it was important for the synthesis of gliotransmitter ATP from adenosine. This would be consistent with a previously noted delay in transmitter release of ATP in astrocytes but not in neurons. The present study has confirmed and quantitated stimulated ATP release in response to glutamate, adenosine, or an elevated K + concentration from well-differentiated astrocyte cultures, measured by a luciferin–luciferase reaction. It showed that the stimulated ATP release was abolished by downregulation of ENT3 with small interfering RNA (siRNA), regardless of the stimulus. The concept that transmitter ATP in mature astrocytes is synthesized directly from adenosine prior to release is supported by the postnatal development of the expression of the vesicular transporter SLC17A9 in astrocytes. In neurons, this transporter carries ATP into synaptic vesicles, but in astrocytes, its expression is pronounced only in immature cells and shows a rapid decline during the first 3 postnatal weeks so that it has almost disappeared at the end of the third week in well-differentiated astrocytes, where its role has probably been taken over by ENT3.https://doi.org/10.1177/1759091414543439 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dan Song Junnan Xu Qiufang Bai Liping Cai Leif Hertz Liang Peng |
spellingShingle |
Dan Song Junnan Xu Qiufang Bai Liping Cai Leif Hertz Liang Peng Role of the Intracellular Nucleoside Transporter ENT3 in Transmitter and High K Stimulation of Astrocytic ATP Release Investigated Using siRNA Against ENT3 ASN Neuro |
author_facet |
Dan Song Junnan Xu Qiufang Bai Liping Cai Leif Hertz Liang Peng |
author_sort |
Dan Song |
title |
Role of the Intracellular Nucleoside Transporter ENT3 in Transmitter and High K Stimulation of Astrocytic ATP Release Investigated Using siRNA Against ENT3 |
title_short |
Role of the Intracellular Nucleoside Transporter ENT3 in Transmitter and High K Stimulation of Astrocytic ATP Release Investigated Using siRNA Against ENT3 |
title_full |
Role of the Intracellular Nucleoside Transporter ENT3 in Transmitter and High K Stimulation of Astrocytic ATP Release Investigated Using siRNA Against ENT3 |
title_fullStr |
Role of the Intracellular Nucleoside Transporter ENT3 in Transmitter and High K Stimulation of Astrocytic ATP Release Investigated Using siRNA Against ENT3 |
title_full_unstemmed |
Role of the Intracellular Nucleoside Transporter ENT3 in Transmitter and High K Stimulation of Astrocytic ATP Release Investigated Using siRNA Against ENT3 |
title_sort |
role of the intracellular nucleoside transporter ent3 in transmitter and high k stimulation of astrocytic atp release investigated using sirna against ent3 |
publisher |
SAGE Publishing |
series |
ASN Neuro |
issn |
1759-0914 |
publishDate |
2014-07-01 |
description |
This study investigates the role of the intracellular adenosine transporter equilibrative nucleoside transporter 3 (ENT3) in stimulated release of the gliotransmitter adenosine triphosphate (ATP) from astrocytes. Within the past 20 years, our understanding of the importance of astrocytic handling of adenosine, its phosphorylation to ATP, and release of astrocytic ATP as an important transmitter has become greatly expanded. A recent demonstration that the mainly intracellular nucleoside transporter ENT3 shows much higher expression in freshly isolated astrocytes than in a corresponding neuronal preparation leads to the suggestion that it was important for the synthesis of gliotransmitter ATP from adenosine. This would be consistent with a previously noted delay in transmitter release of ATP in astrocytes but not in neurons. The present study has confirmed and quantitated stimulated ATP release in response to glutamate, adenosine, or an elevated K + concentration from well-differentiated astrocyte cultures, measured by a luciferin–luciferase reaction. It showed that the stimulated ATP release was abolished by downregulation of ENT3 with small interfering RNA (siRNA), regardless of the stimulus. The concept that transmitter ATP in mature astrocytes is synthesized directly from adenosine prior to release is supported by the postnatal development of the expression of the vesicular transporter SLC17A9 in astrocytes. In neurons, this transporter carries ATP into synaptic vesicles, but in astrocytes, its expression is pronounced only in immature cells and shows a rapid decline during the first 3 postnatal weeks so that it has almost disappeared at the end of the third week in well-differentiated astrocytes, where its role has probably been taken over by ENT3. |
url |
https://doi.org/10.1177/1759091414543439 |
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