title: L-trans-PDC enhances hippocampal neuronal activity by stimulating glial glutamate release independently of blocking transporters.
abstract: The glutamate transporter inhibitor, L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) reversibly enhanced hippocampal neuronal activity in the rat and mouse dentate gyrus. The PDC action was still found in mice lacking the glial glutamate transporter GLT-1. PDC did not influence the rate of spontaneous miniature excitatory postsynaptic currents and spontaneous inhibitory postsynaptic currents, ionotropic glutamate receptor currents, or GABA-evoked currents in cultured rat hippocampal neurons. PDC increased glutamate released from cultured hippocampal astrocytes from normal rats, normal mice, and GLT-1 knock-out mice, that is not inhibited by deleting extracellular Na(+), while the drug had no effect on the release from cultured rat hippocampal neurons. The results of the present study thus suggest that PDC stimulates glial glutamate release by a mechanism independent of inhibiting glutamate transporters, which perhaps causes an increase in synaptic glutamate concentrations, in part responsible for the enhancement in hippocampal neuronal activity.
authors.affiliation: Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Ohta
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Nomura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanno
authors.forename: Kaoru
authors.initials: K
authors.lastname: Nagai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yajima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondoh
authors.forename: Eiji
authors.initials: E
authors.lastname: Kohmura
authors.forename: Naoaki
authors.initials: N
authors.lastname: Saito
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nishizaki
mesh_terms: D000818:Animals; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D013570:Synaptic Membranes / Q000502:physiology
chemical_list: D003998:Dicarboxylic Acids; D011759:Pyrrolidines; D018698:Glutamic Acid; C083486:pyrrolidine-2,4-dicarboxylic acid