title: Blockers of adenosine A1, but not muscarinic acetylcholine, receptors improve excessive extracellular glutamate-induced synaptic depression.
abstract: We investigated adenosinergic and cholinergic effects on excessive glutamate-induced depressions of central excitatory synaptic transmissions in vitro. From the CA1 region in rat hippocampal slices, orthodromically elicited population spikes (PSs) and field excitatory postsynaptic potentials (fEPSPs) at 0.1Hz were simultaneously recorded. ANOVA was used for statistics, and p<0.05 was accepted as significant. Glutamate (10mM for 10min) completely depressed PSs and fEPSPs, which were partially recovered by the following washout for 40min (67.5±15.7% and 65.4±13.9% of the control, respectively, p<0.01, n=12). The recoveries in PSs and fEPSPs were exacerbated by edrophonium and carbamoylcholine but improved by non- and A1-selective adenosine receptor antagonists (p<0.01, n=6). The recovery in PSs, not that in fEPSPs, was exacerbated by adenosine, adenosine A1-receptor agonist and A2a-receptor antagonist (p<0.01, n=6). The effects of edrophonium were blocked by non-, M2- and M4-selective muscarinic acetylcholine receptor antagonists (p<0.01, n=6). Excessive glutamate depresses glutamatergic excitatory synaptic transmissions, which are exacerbated by muscarinic acetylcholine receptor stimulation but improved by adenosine A1 receptor block. Somatic excitability is impaired by excessive glutamate with adenosine A1 receptor stimulation.
authors.affiliation: Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan. enarimat@sapmed.ac.jp
authors.forename: Eichi
authors.initials: E
authors.lastname: Narimatsu
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Niiya
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Takada
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Michiaki
authors.initials: M
authors.lastname: Yamakage
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000241:Adenosine / Q000037:antagonists & inhibitors*; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D011976:Receptors, Muscarinic; D018698:Glutamic Acid; D000241:Adenosine; D000109:Acetylcholine