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

Otsuguro, Ken-ichi; Tomonari, Yuki; Otsuka, Saori; Yamaguchi, Soichiro; Kon, Yasuhiro; Ito, Shigeo

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

Otsuguro, Ken-ichi; Tomonari, Yuki; Otsuka, Saori et al.

Neuropharmacology, 2015, 97, 160-170

Permalink : https://hdl.handle.net/2115/62927

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アクセス権	open access
URI	https://hdl.handle.net/2115/62927
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 ; Tomonari, Yuki ; Otsuka, Saori ; Yamaguchi, Soichiro ; Kon, Yasuhiro ; Ito, Shigeo
e-Rad_Researcher 40344494 著者名 Otsuguro, Ken-ichi
著者名 Tomonari, Yuki
e-Rad_Researcher 10566152 著者名 Otsuka, Saori
e-Rad_Researcher 50596864 著者名 Yamaguchi, Soichiro
e-Rad_Researcher 10178402 著者名 Kon, Yasuhiro
e-Rad_Researcher 40109509 著者名 Ito, Shigeo
言語	英語
キーワード	Adenosine kinase inhibitor
	Equilibrative nucleoside transporter
	Spinal cord
	Reflex potential
	Adenosine
	A(1) receptor
発行日	2015-10
出版者	Elsevier
収録物名	Neuropharmacology
巻(号)	97
ページ	160-170
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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	©2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0028-3908
EISSN	1873-7064
NCID	AA00754812
関連情報	PMID 26066576
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.neuropharm.2015.05.035