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

作者: Ken-ichi Otsuguro , Yuki Tomonari , Saori Otsuka , Soichiro Yamaguchi , Yasuhiro Kon

DOI: 10.1016/J.NEUROPHARM.2015.05.035

关键词: EndocrinologyPurinergic signallingEquilibrative nucleoside transporterChemistryEHNAAdenosine A3 receptorAdenosine kinaseInternal medicineAdenosine A1 receptorAdenosine receptorAdenosine

摘要: 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, non-nucleoside inhibitor, shows analgesic effect in animal models pain. Here, we investigated the ABT-702 on synaptic transmission via nociceptive and reflex pathways isolated spinal cord neonatal rats. The release adenosine from was measured by HPLC. inhibited slow ventral root potentials (sVRPs) pathway more potently than monosynaptic (MSRs) pathway. inhibitory were mimicked exogenously applied adenosine, blocked 8CPT (8-cyclopentyl-1,3-dipropylxanthine), an A1 receptor antagonist, augmented EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), deaminase (ADA) inhibitor. Equilibrative nucleoside transporter (ENT) reversed not those adenosine. released cord, that also ENT inhibitors. ABT-702-facilitated way ENTs inhibits activation receptors. This feature expected to lead good effects, but, caution may be required use case ADA dysfunction or combination with

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