title: ENT1 inhibition attenuates epileptic seizure severity via regulation of glutamatergic neurotransmission.
abstract: Type 1 equilibrative nucleoside transporter (ENT1) promotes glutamate release by inhibition of adenosine signaling. However, whether ENT1 plays a role in epileptic seizure that involves elevated glutamatergic neurotransmission is unknown. Here, we report that both seizure rats and patients show increased expression of ENT1. Intrahippocampal injection of a specific inhibitor of ENT1, nitrobenzylthioinosine (NBTI), attenuates seizure severity and prolongs onset latency. In order to examine whether NBTI would be effective as antiepileptic after peripheral application, we injected NBTI intraperitoneally, and the results were similar to those obtained after intrahippocampal injection. NBTI administration leads to suppressed neuronal firing in seizure rats. In addition, increased mEPSC in seizure are inhibited by NBTI. Finally, NBTI results in deactivation of phosphorylated cAMP-response element-binding protein in the seizure rats. These results indicate that ENT1 plays an important role in the development of seizure. Inhibition of ENT1 might provide a novel therapeutic approach toward the control of epileptic seizure.
authors.affiliation: Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, China.
authors.forename: Zucai
authors.initials: Z
authors.lastname: Xu
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.forename: Yalan
authors.initials: Y
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Yanke
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yaodong
authors.initials: Y
authors.lastname: Lv
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Kewei
authors.initials: K
authors.lastname: Wang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.forename: Guojun
authors.initials: G
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000502:physiology; D000293:Adolescent; D000328:Adult; D000818:Animals; D038481:Anterior Temporal Lobectomy; D000927:Anticonvulsants / Q000627:therapeutic use; D056547:CA1 Region, Hippocampal / Q000737:chemistry / Q000473:pathology; D002352:Carrier Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D002675:Child, Preschool; D003292:Convulsants / Q000633:toxicity; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004195:Disease Models, Animal; D004351:Drug Resistance; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D033721:Equilibrative Nucleoside Transporter 1 / Q000032:analysis / Q000502:physiology*; D005971:Glutamates / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010862:Pilocarpine / Q000633:toxicity; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D002352:Carrier Proteins; D003292:Convulsants; D017362:Cyclic AMP Response Element-Binding Protein; D033721:Equilibrative Nucleoside Transporter 1; D005971:Glutamates; D009419:Nerve Tissue Proteins; C438649:SLC29A1 protein, human; C438652:Slc29a1 protein, rat; D010862:Pilocarpine; D013868:Thioinosine; C001789:4-nitrobenzylthioinosine; D000241:Adenosine