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Mutual role of ecto-5'-nucleotidase/CD73 and concentrative nucleoside transporter 3 in the intestinal uptake of dAMP
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Title: | Mutual role of ecto-5'-nucleotidase/CD73 and concentrative nucleoside transporter 3 in the intestinal uptake of dAMP |
Authors: | Narumi, Katsuya Browse this author →KAKEN DB | Ohata, Tsukika Browse this author | Horiuchi, Yuichi Browse this author | Satoh, Hiroshi Browse this author | Furugen, Ayako Browse this author →KAKEN DB | Kobayashi, Masaki Browse this author →KAKEN DB | Iseki, Ken Browse this author →KAKEN DB |
Issue Date: | 21-Oct-2019 |
Publisher: | PLOS |
Journal Title: | PLoS ONE |
Volume: | 14 |
Issue: | 10 |
Start Page: | e0223892 |
Publisher DOI: | 10.1371/journal.pone.0223892 |
Abstract: | 2'-Deoxyadenosine 5'-monophosphate (dAMP), a deoxyribonucleotide found in DNA, affects intestinal cell growth. The molecular mechanisms underlying gastrointestinal absorption of foreign DNA ingested along with food has hardly been investigated. The aim of this study was to investigate the mechanism underlying intestinal absorption of dAMP. The uptake of [H-3]dAMP by Caco-2 cells was Na+- and pH-dependent and was inhibited by various nucleosides. In contrast, nitrobenzylthioinosine (NMBPR), an equilibrative nucleoside transporter inhibitor, showed little inhibitory effects on [H-3]dAMP uptake. Additionally, human concentrative nucleoside transporter (CNT) 3, transiently expressed in COS-7 cells, mediated the uptake of [3H]dAMP. A kinetic study revealed that the K-m value of CNT3-mediated uptake of dAMP (59.6 mu M) was close to that of 2'-deoxyadenosine (dAdo) (56.3 mu M), whereas the dAMP V-max (15.6 pmol.mg protein(-1)min(-1)) was 500-fold lesser than the dAdo V-max (7782 pmol.mg protein-1min-1). Further, [3H]dAMP uptake was greater in COS-7 cells expressing ecto-5'-nucleotidase/CD73 with CNT3 than in those expressing CNT3 alone. These data suggest that, although dAMP is a substrate of CNT3, it is dephosphorylated to dAdo by CD73 and is efficiently absorbed as dAdo from the intestinal lumen. |
Rights: | https://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/78560 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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