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J Neurosci
1997 Aug 01;1715:5760-71. doi: 10.1523/JNEUROSCI.17-15-05760.1997.
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A novel allosteric potentiator of AMPA receptors: 4--2-(phenylsulfonylamino)ethylthio--2,6-difluoro-phenoxyaceta mide.
Sekiguchi M, Fleck MW, Mayer ML, Takeo J, Chiba Y, Yamashita S, Wada K.
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We report that a novel sulfonylamino compound, 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetam ide (PEPA), selectively potentiates glutamate receptors of the AMPA subtype. PEPA (1-200 microM) dose dependently potentiated glutamate-evoked currents in Xenopus oocytes expressing AMPA (GluRA-GluRD), but not kainate (GluR6 and GluR6+KA2) or NMDA (zeta1 + epsilon1-epsilon4), receptor subunits. PEPA was effective at micromolar concentrations and, in contrast to the action of cyclothiazide, preferentially modulated AMPA receptor flop isoforms. At 200 microM, PEPA potentiated glutamate responses by 50-fold in oocytes expressing GluRCflop (EC50 approximately 50 microM) versus only threefold for GluRCflip; a similar preference for flop isoforms was observed for other AMPA receptor subunits. Dose-response analysis for GluRCflop revealed that 100 microM PEPA produced a sevenfold increase in AMPA receptor affinity for glutamate. PEPA produced considerably weaker potentiation of kainate-evoked than glutamate-evoked currents, suggesting modulation of the process of receptor desensitization. In human embryonic kidney 293 cells transfected with AMPA receptor subunits, PEPA either abolished or markedly slowed the rate of onset of desensitization and potentiated steady-state equilibrium currents evoked by glutamate with subunit (GluRC >/= GluRD > GluRA) and splice-variant (flop > flip) selectivity similar to that observed in oocytes. Our results show that PEPA is a novel, flop-preferring allosteric modulator of AMPA receptor desensitization at least 100 times more potent than aniracetam.
Arai,
A centrally active drug that modulates AMPA receptor gated currents.
1994, Pubmed
Arai,
A centrally active drug that modulates AMPA receptor gated currents.
1994,
Pubmed Bennett,
Topology profile for a glutamate receptor: three transmembrane domains and a channel-lining reentrant membrane loop.
1995,
Pubmed
,
Xenbase Bertolino,
Modulation of AMPA/kainate receptors by analogues of diazoxide and cyclothiazide in thin slices of rat hippocampus.
1993,
Pubmed Boulter,
Molecular cloning and functional expression of glutamate receptor subunit genes.
1990,
Pubmed
,
Xenbase Bowie,
Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block.
1995,
Pubmed Chen,
High-efficiency transformation of mammalian cells by plasmid DNA.
1987,
Pubmed Diamond,
Asynchronous release of synaptic vesicles determines the time course of the AMPA receptor-mediated EPSC.
1995,
Pubmed Ferrer-Montiel,
Pentameric subunit stoichiometry of a neuronal glutamate receptor.
1996,
Pubmed
,
Xenbase Fleck,
AMPA receptor heterogeneity in rat hippocampal neurons revealed by differential sensitivity to cyclothiazide.
1996,
Pubmed Hestrin,
Activation and desensitization of glutamate-activated channels mediating fast excitatory synaptic currents in the visual cortex.
1992,
Pubmed Hollmann,
Cloning by functional expression of a member of the glutamate receptor family.
1989,
Pubmed
,
Xenbase Hollmann,
Ca2+ permeability of KA-AMPA--gated glutamate receptor channels depends on subunit composition.
1991,
Pubmed
,
Xenbase Hollmann,
N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluR1.
1994,
Pubmed
,
Xenbase Hume,
Identification of a site in glutamate receptor subunits that controls calcium permeability.
1991,
Pubmed
,
Xenbase Isaacson,
Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents in the hippocampus.
1991,
Pubmed
,
Xenbase Ito,
Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.
1990,
Pubmed
,
Xenbase Johansen,
Interactions among GYKI-52466, cyclothiazide, and aniracetam at recombinant AMPA and kainate receptors.
1995,
Pubmed
,
Xenbase Keinänen,
A family of AMPA-selective glutamate receptors.
1990,
Pubmed Lomeli,
Control of kinetic properties of AMPA receptor channels by nuclear RNA editing.
1994,
Pubmed
,
Xenbase Matsui,
Functional comparison of D-serine and glycine in rodents: the effect on cloned NMDA receptors and the extracellular concentration.
1995,
Pubmed
,
Xenbase Monyer,
Glutamate-operated channels: developmentally early and mature forms arise by alternative splicing.
1991,
Pubmed Mosbacher,
A molecular determinant for submillisecond desensitization in glutamate receptors.
1994,
Pubmed
,
Xenbase Otis,
Direct measurement of AMPA receptor desensitization induced by glutamatergic synaptic transmission.
1996,
Pubmed Partin,
Structural determinants of allosteric regulation in alternatively spliced AMPA receptors.
1995,
Pubmed
,
Xenbase Partin,
Cyclothiazide differentially modulates desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor splice variants.
1994,
Pubmed
,
Xenbase Partin,
AMPA receptor flip/flop mutants affecting deactivation, desensitization, and modulation by cyclothiazide, aniracetam, and thiocyanate.
1996,
Pubmed Patneau,
Hippocampal neurons exhibit cyclothiazide-sensitive rapidly desensitizing responses to kainate.
1993,
Pubmed Patneau,
Kinetic analysis of interactions between kainate and AMPA: evidence for activation of a single receptor in mouse hippocampal neurons.
1991,
Pubmed Raman,
Pathway-specific variants of AMPA receptors and their contribution to neuronal signaling.
1994,
Pubmed Sato,
Synthesis and evaluation of novel thiazolidine derivatives as thromboxane A2 receptor antagonists.
1994,
Pubmed Sekiguchi,
A deletion in the second cytoplasmic loop of GluR3 produces a dominant negative mutant of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor.
1994,
Pubmed
,
Xenbase Sommer,
Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS.
1990,
Pubmed Sommer,
RNA editing in brain controls a determinant of ion flow in glutamate-gated channels.
1991,
Pubmed Staubli,
Facilitation of glutamate receptors enhances memory.
1994,
Pubmed Stäubli,
Centrally active modulators of glutamate receptors facilitate the induction of long-term potentiation in vivo.
1994,
Pubmed Stein,
Complex pharmacological properties of recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subtypes.
1992,
Pubmed
,
Xenbase Stern-Bach,
Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins.
1994,
Pubmed
,
Xenbase Sutcliffe,
Three-dimensional models of non-NMDA glutamate receptors.
1996,
Pubmed Swanson,
Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition.
1997,
Pubmed Tang,
Modulation of the time course of fast EPSCs and glutamate channel kinetics by aniracetam.
1991,
Pubmed Trussell,
Desensitization of AMPA receptors upon multiquantal neurotransmitter release.
1993,
Pubmed Trussell,
Glutamate receptor desensitization and its role in synaptic transmission.
1989,
Pubmed Tsuzuki,
Agonist- and subunit-dependent potentiation of glutamate receptors by a nootropic drug aniracetam.
1992,
Pubmed
,
Xenbase Verdoorn,
Structural determinants of ion flow through recombinant glutamate receptor channels.
1991,
Pubmed Vyklicky,
Modulation of excitatory synaptic transmission by drugs that reduce desensitization at AMPA/kainate receptors.
1991,
Pubmed Wenthold,
Immunochemical characterization of the non-NMDA glutamate receptor using subunit-specific antibodies. Evidence for a hetero-oligomeric structure in rat brain.
1992,
Pubmed Yamada,
Benzothiadiazides inhibit rapid glutamate receptor desensitization and enhance glutamatergic synaptic currents.
1993,
Pubmed Yamada,
Diazoxide blocks glutamate desensitization and prolongs excitatory postsynaptic currents in rat hippocampal neurons.
1992,
Pubmed Zivkovic,
7-Chloro-3-methyl-3-4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide (IDRA 21): a benzothiadiazine derivative that enhances cognition by attenuating DL-alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) receptor desensitization.
1995,
Pubmed
