Modulation of fast excitatory synaptic transmission by cyclothiazide and GYKI 52466 in the rat hippocampus.
The effects of cyclothiazide, a drug which potentiates AMPA receptor-mediated responses and GYKI 52466, a non-competitive AMPA receptor antagonist, were studied on fast glutamatergic transmission in rat hippocampal slices. Cyclothiazide prolonged the decay of AMPA receptor-mediated EPSCs (AMPA-EPSCs) in a concentration-dependent manner. GYKI 52466 reduced the peak amplitude of AMPA-EPSCs and blocked the induction of LTP. When GYKI 52466 was applied in the presence of cyclothiazide it still reduced the peak amplitude of AMPA-EPSCs but was not able to reverse the cyclothiazide induced prolongation of AMPA-EPSC duration. These data suggest that GYKI 52466 and cyclothiazide probably mediate their effects on the AMPA receptor via different binding sites.
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, FRG.
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G
Rammes
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C
Parsons
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W
Müller
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Swandulla
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents; D000959:Antihypertensive Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D001581:Benzothiadiazines / Q000494:pharmacology*; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects*
D015763:2-Amino-5-phosphonovalerate; D014151:Anti-Anxiety Agents; D000959:Antihypertensive Agents; D001569:Benzodiazepines; D001581:Benzothiadiazines; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D010852:Picrotoxin; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C061950:GYKI 52466; C066430:CGP 35348; C004639:cyclothiazide