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.
Rammes
G
G
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, FRG.
Parsons
C
C
Müller
W
W
Swandulla
D
D
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