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An adenosine kinase inhibitor, ABT-702, inhibits spinal nociceptive transmission by adenosine release via equilibrative nucleoside transporters in rat

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Neuropharmacology_v.97p.160-70.pdf1.01 MBPDF見る/開く
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タイトル: An adenosine kinase inhibitor, ABT-702, inhibits spinal nociceptive transmission by adenosine release via equilibrative nucleoside transporters in rat
著者: Otsuguro, Ken-ichi 著作を一覧する
Tomonari, Yuki 著作を一覧する
Otsuka, Saori 著作を一覧する
Yamaguchi, Soichiro 著作を一覧する
Kon, Yasuhiro 著作を一覧する
Ito, Shigeo 著作を一覧する
キーワード: Adenosine kinase inhibitor
Equilibrative nucleoside transporter
Spinal cord
Reflex potential
Adenosine
A(1) receptor
発行日: 2015年10月
出版者: Elsevier
誌名: Neuropharmacology
巻: 97
開始ページ: 160
終了ページ: 170
出版社 DOI: 10.1016/j.neuropharm.2015.05.035
抄録: Adenosine kinase (AK) inhibitor is a potential candidate for controlling pain, but some AK inhibitors have problems of adverse effects such as motor impairment. ABT-702, a non-nucleoside AK inhibitor, shows analgesic effect in animal models of pain. Here, we investigated the effects of ABT-702 on synaptic transmission via nociceptive and motor reflex pathways in the isolated spinal cord of neonatal rats. The release of adenosine from the spinal cord was measured by HPLC. ABT-702 inhibited slow ventral root potentials (sVRPs) in the nociceptive pathway more potently than monosynaptic reflex potentials (MSRs) in the motor reflex pathway. The inhibitory effects of ABT-702 were mimicked by exogenously applied adenosine, blocked by 8CPT (8-cyclopentyl-1,3-dipropylxanthine), an adenosine A(1) receptor antagonist, and augmented by EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), an adenosine deaminase (ADA) inhibitor. Equilibrative nucleoside transporter (ENT) inhibitors reversed the effects of ABT-702, but not those of adenosine. ABT-702 released adenosine from the spinal cord, an effect that was also reversed by ENT inhibitors. The ABT-702-facilitated release of adenosine by way of ENTs inhibits nociceptive pathways more potently than motor reflex pathways in the spinal cord via activation of A1 receptors. This feature is expected to lead to good analgesic effects, but, caution may be required for the use of AK inhibitors in the case of ADA dysfunction or a combination with ENT inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.
Rights: ©2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
資料タイプ: article (author version)
URI: http://hdl.handle.net/2115/62927
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 乙黒 兼一

 

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