title: Exendin (5-39), an antagonist of GLP-1 receptor, modulates synaptic transmission via glutamate uptake in the dentate gyrus.
abstract: Extracellular concentrations of glutamate are mainly controlled by an astrocytic glutamate transporter, GLT-1. We previously reported that exendin (5-39) (Ex), an antagonist of the GLP-1 receptor, improved memory impairment in β-amyloid protein-treated rats. In this study, we investigated effects of Ex on synaptic transmission through astrocytic GLT-1 in the hippocampus. Continuous intracerebroventricular (i.c.v.) administration of Ex for 1-week increased GLT-1 protein levels in the hippocampus of 4-week-old male Wistar rats. For electrophysiological studies, hippocampal slices were prepared from these Ex-treated rats or vehicle-treated rats. Ex decreased fEPSP decay time, and increased the input-output relation and decreased the paired-pulse ratio in the dentate gyrus (DG). Furthermore, Ex inhibited long-term depression but not long-term potentiation in the DG. These effects were prevented by DHK, a specific GLT-1 inhibitor. In addition, glutamate uptake was significantly increased by Ex-treatment in cultured astrocytes. These results suggest that Ex modulates synaptic transmission and plasticity through astrocytic glutamate uptake in the DG.
authors: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors: Kazuma
authors: K
authors: Kobayashi
authors: Takashi
authors: T
authors: Iwai
authors: Sachie
authors: S
authors: Sasaki-Hamada
authors: Gaku
authors: G
authors: Kamanaka
authors: Jun-Ichiro
authors: J
authors: Oka
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects*; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D000067757:Glucagon-Like Peptide-1 Receptor; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D018690:Excitatory Amino Acid Agonists; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D012333:RNA, Messenger; D018027:Receptors, Glucagon; C417195:exendin (5-39); D018698:Glutamic Acid; C020889:dihydrokainic acid; D007608:Kainic Acid