Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Br J Pharmacol
2002 Aug 01;1367:1033-41. doi: 10.1038/sj.bjp.0704804.
Show Gene links
Show Anatomy links
A desensitization-selective potentiator of AMPA-type glutamate receptors.
Sekiguchi M
,
Nishikawa K
,
Aoki S
,
Wada K
.
???displayArticle.abstract???
1: We examined the effects of PEPA, an allosteric potentiator of AMPA receptors, on AMPA receptor kinetics. 2: PEPA did not affect the deactivation of glutamate responses but potently attenuated the extent of receptor desensitization without slowing the onset of desensitization in most of the recombinant AMPA receptors (GluR1-flip, GluR1-flop, GluR3-flip, GluR3-flip+GluR2-flip, and GluR3-flop+GluR2-flop) expressed in Xenopus oocytes. For the GluR3-flop subunit, PEPA attenuated the extent of desensitization and only weakly prolonged deactivation (1.3 fold). 3: PEPA did not significantly affect recovery from desensitization in oocytes expressing GluR3-flip, GluR1-flop, and GluR1-flop, but weakly accelerated (2.6 fold) recovery from desensitization in oocytes expressing GluR3-flop. 4: PEPA's effect on desensitization of GluR3-flop-containing receptors is unique in that onset is very slow. 5: Simulation studies using simplified kinetic models for AMPA receptors are utilized to explore the differential effects of PEPA on GluR3-flip and -flop. It is possible to simulate the action on GluR3-flip by modulating two rate constants in a 12-state kinetic model. For simulation of the action on GluR3-flop, the 12-state kinetic model is not enough, and it is necessary to invoke a 13th state, a PEPA-bound receptor to which glutamate cannot bind. 6: These results suggest that attenuation of extent of desensitization represents the principal mechanism underlying the potentiation of AMPA receptors by PEPA, and that PEPA exhibits different mechanisms with respect to GluR3-flip and GluR3-flop.
Arai,
Effects of a memory-enhancing drug on DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor currents and synaptic transmission in hippocampus.
1996, Pubmed
Arai,
Effects of a memory-enhancing drug on DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor currents and synaptic transmission in hippocampus.
1996,
Pubmed
Arai,
Effects of the potent ampakine CX614 on hippocampal and recombinant AMPA receptors: interactions with cyclothiazide and GYKI 52466.
2000,
Pubmed
Arai,
The waveform of synaptic transmission at hippocampal synapses is not determined by AMPA receptor desensitization.
1998,
Pubmed
Arai,
Effects of a centrally active benzoylpyrrolidine drug on AMPA receptor kinetics.
1996,
Pubmed
Benveniste,
A kinetic analysis of the modulation of N-methyl-D-aspartic acid receptors by glycine in mouse cultured hippocampal neurones.
1990,
Pubmed
Cumin,
Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents.
1982,
Pubmed
Hampson,
Facilitative effects of the ampakine CX516 on short-term memory in rats: enhancement of delayed-nonmatch-to-sample performance.
1998,
Pubmed
Hampson,
Facilitative effects of the ampakine CX516 on short-term memory in rats: correlations with hippocampal neuronal activity.
1998,
Pubmed
Howe,
Currents through single glutamate receptor channels in outside-out patches from rat cerebellar granule cells.
1991,
Pubmed
Lynch,
Evidence that a positive modulator of AMPA-type glutamate receptors improves delayed recall in aged humans.
1997,
Pubmed
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
Raman,
The mechanism of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor desensitization after removal of glutamate.
1995,
Pubmed
Sekiguchi,
Pharmacological detection of AMPA receptor heterogeneity by use of two allosteric potentiators in rat hippocampal cultures.
1998,
Pubmed
,
Xenbase
Sekiguchi,
A novel allosteric potentiator of AMPA receptors: 4--2-(phenylsulfonylamino)ethylthio--2,6-difluoro-phenoxyaceta mide.
1997,
Pubmed
,
Xenbase
Sekiguchi,
The AMPA receptor allosteric potentiator PEPA ameliorates post-ischemic memory impairment.
2001,
Pubmed
Shen,
Modulation of desensitization at glutamate receptors in isolated crucian carp horizontal cells by concanavalin A, cyclothiazide, aniracetam and PEPA.
1999,
Pubmed
,
Xenbase
Shen,
Characterization of AMPA receptors on isolated amacrine-like cells in carp retina.
1999,
Pubmed
,
Xenbase
Shen,
Zinc modulation of AMPA receptors may be relevant to splice variants in carp retina.
1999,
Pubmed
,
Xenbase
Staubli,
Facilitation of glutamate receptors enhances memory.
1994,
Pubmed
Thompson,
7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys.
1995,
Pubmed
Vanover,
Effects of AMPA receptor positive modulators on amphetamine- and dizocilpine-induced locomotion.
1997,
Pubmed
Verdoorn,
Structural determinants of ion flow through recombinant glutamate receptor channels.
1991,
Pubmed
Yamada,
The diazoxide derivative 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine-S,S-dioxide augments AMPA- and GABA-mediated synaptic responses in cultured hippocampal neurons.
1998,
Pubmed
Yamada,
Modulating excitatory synaptic neurotransmission: potential treatment for neurological disease?
1998,
Pubmed
