Allosteric interactions between cyclothiazide and AMPA/kainate receptor antagonists

Yamada, Kelvin A.; Turetsky, Dorothy M.

doi:10.1111/j.1476-5381.1996.tb15337.x

Cited by 45 publications

(24 citation statements)

References 31 publications

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“…Cyclothiazide CTZ selectively blocks desensitization of AMPA receptors, and therefore causes massive potentiation of the responses, both in recombinant and naturally expressed receptors (Partin et al, 1993;Wong & Mayer, 1993;Wilding & Huettner, 1995;Yamada & Turetsky, 1996). Our results show that CTZ concentration-dependently potentiated responses to AMPA of both types of neurones.…”

Section: Kinetic and Rectifying Properties Of Responses Evoked By Rapsupporting

confidence: 57%

“…Studies on recombinant receptors show that the action of CTZ is highly dependent on the subunit composition, the splice variants (Sekiguchi et al, 1998) and the editing status (Yamada & Turetsky, 1996;Fleck et al, 1996). Studies on the eect of CTZ on homomerically expressed AMPA receptors showed a wide range of potentiation, with ratios of 102 fold for GluR1 i , 27 fold for GluR2 i , 216 fold for GluR3 i and 16 fold for GluR4 i (Yamada & Turetsky, 1996).…”

Section: Kinetic and Rectifying Properties Of Responses Evoked By Rapmentioning

confidence: 99%

“…Studies on the eect of CTZ on homomerically expressed AMPA receptors showed a wide range of potentiation, with ratios of 102 fold for GluR1 i , 27 fold for GluR2 i , 216 fold for GluR3 i and 16 fold for GluR4 i (Yamada & Turetsky, 1996). Although¯ip variants desensitize to a lesser degree than¯op variants, they nevertheless have a higher anity for CTZ (Fleck et al, 1996) and exhibit a greater degree of potentiation (Sekiguchi et al, 1998).…”

Section: Kinetic and Rectifying Properties Of Responses Evoked By Rapmentioning

confidence: 99%

“…Cyclothiazide (CTZ) blocks desensitization of AMPA receptors, while responses mediated by KA receptors are unaected, or slightly depressed (Partin et al, 1993;Wilding & Huettner, 1995;Yamada & Turetsky, 1996). Studies on recombinant AMPA receptors have shown that CTZ reduces the desensitization of ip splice variants more than¯op variants (Partin et al, 1993;Fleck et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Characteristics of AMPA receptor‐mediated responses of cultured cortical and spinal cord neurones and their correlation to the expression of glutamate receptor subunits, GluR1‐4

Dai

Egebjerg

Lambert

2001

British J Pharmacology

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1 Electrophysiological recordings have been used to characterize responses mediated by AMPA receptors expressed by cultured rat cortical and spinal cord neurones. The EC 50 values for AMPA were 17 and 11 mM, respectively. 2 Responses of cortical neurones to AMPA were inhibited competitively by NBQX (pK i =6.6). Lower concentrations of NBQX (41 mM) also potentiated the plateau responses of spinal cord neurones to AMPA, which could be attributed to a depression of desensitization to AMPA. 3 GYKI 52466 inhibited responses of spinal cord neurones to AMPA to about twice the extent of responses of cortical neurones. 4 Blockade of AMPA receptor desensitization by cyclothiazide (CTZ) potentiated responses of spinal cord neurones (6.8 fold) signi®cantly more than responses of cortical neurones (4.8 fold). Responses of cortical neurones to KA were potentiated 3.5 fold by CTZ, while responses of spinal cord neurones were unaected. 5 Ultra-fast applications of AMPA to outside-out patches showed responses of spinal cord neurones desensitized by 97.5% and exhibit marked inward recti®cation, whereas cortical neurones desensitized by 91% and exhibited slight outward recti®cation. The time constants of deactivation and desensitization were about twice as fast in spinal cord than cortical neurones. 6 In cortical neurones, single-cell RT ± PCR showed GluR2 and GluR1 accounted for 91% of all subunits and were expressed together in 67% of neurones, predominantly as the¯ip variants (78%). GluR2 was detected alone in 24% of neurones. GluR3 and GluR4 were present in only 14 and 29% of neurones, respectively. For spinal cord neurones, GluR4 o was detected in 81% of neurones, whereas predominantly¯op versions of GluR1, 2 and 3 were detected in 38, 13 and 13% of neurones, respectively. These expression patterns are related to the respective pharmacological and mechanistic properties.

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Section: Kinetic and Rectifying Properties Of Responses Evoked By Rapsupporting

confidence: 57%

Section: Kinetic and Rectifying Properties Of Responses Evoked By Rapmentioning

confidence: 99%

Section: Kinetic and Rectifying Properties Of Responses Evoked By Rapmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Characteristics of AMPA receptor‐mediated responses of cultured cortical and spinal cord neurones and their correlation to the expression of glutamate receptor subunits, GluR1‐4

Dai

Egebjerg

Lambert

2001

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…The functional effects of the different positive allosteric modulators are complex because multiple partially overlapping binding sites exist (Partin et al, 1996;Yamada and Turetsky, 1996;Lindén et al, 2001;Arai et al, 2002;Sun et al, 2002). The binding sites of compounds that affect desensitization reside within the dimer interface between the ligand binding domains, which supports the interpretation that desensitization involves rearrangement of the dimer interface.…”

Section: A Positive and Negative Allosteric Modulatorsmentioning

confidence: 49%