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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)
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Submitter: 乙黒 兼一
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