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Different mechanisms of extracellular adenosine accumulation by reduction of the external Ca2+ concentration and inhibition of adenosine metabolism in spinal astrocytes

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Title: Different mechanisms of extracellular adenosine accumulation by reduction of the external Ca2+ concentration and inhibition of adenosine metabolism in spinal astrocytes
Authors: Eguchi, Ryota Browse this author
Akao, Sanae Browse this author
Otsuguro, Ken-ichi Browse this author →KAKEN DB
Yamaguchi, Soichiro Browse this author →KAKEN DB
Ito, Shigeo Browse this author →KAKEN DB
Keywords: ATP
Gap junction hemichannels
Nucleoside transporters
Adenosine kinase
Adenosine deaminase
Issue Date: May-2015
Publisher: 日本薬理学会
Journal Title: Journal of pharmacological sciences
Volume: 128
Issue: 1
Start Page: 47
End Page: 53
Publisher DOI: 10.1016/j.jphs.2015.04.008
PMID: 26003082
Abstract: Extracellular adenosine is a neuromodulator in the central nervous system. Astrocytes mainly participate in adenosine production, and extracellular adenosine accumulates under physiological and pathophysiological conditions. Inhibition of intracellular adenosine metabolism and reduction of the external Ca2+ concentration ([Ca2+](e)) participate in adenosine accumulation, but the precise mechanisms remain unclear. This study investigated the mechanisms underlying extracellular adenosine accumulation in cultured rat spinal astrocytes. The combination of adenosine kinase and deaminase (ADK/ADA) inhibition and a reduced [Ca2+](e) increased the extracellular adenosine level. ADK/ADA inhibitors increased the level of extracellular adenosine but not of adenine nucleotides, which was suppressed by inhibition of equilibrative nucleoside transporter (ENT) 2. Unlike ADK/ADA inhibition, a reduced [Ca2+](e) increased the extracellular level not only of adenosine but also of ATP. This adenosine increase was enhanced by ENT2 inhibition, and suppressed by sodium polyoxotungstate (ecto-nucleoside triphosphate diphosphohydrolase inhibitor). Gap junction inhibitors suppressed the increases in adenosine and adenine nucleotide levels by reduction of [Ca2+](e). These results indicate that extracellular adenosine accumulation by ADK/ADA inhibition is due to the adenosine release via ENT2, while that by reduction of [Ca2+] e is due to breakdown of ATP released via gap junction hemichannels, after which ENT2 incorporates adenosine into the cells. (C) 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
Rights: http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article
URI: http://hdl.handle.net/2115/59983
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 乙黒 兼一

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