CAMP-Dependent protein kinase A activity modulates topiramate potentiation of GABA A receptors

Timothy A. Simeone; Karen S. Wilcox; H. Steve White

doi:10.1016/j.eplepsyres.2011.05.009

CAMP-Dependent protein kinase A activity modulates topiramate potentiation of GABA _A receptors

Timothy A. Simeone, Karen S. Wilcox, H. Steve White

Department of Pharmacology and Neuroscience

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Activation of cAMP-dependent protein kinase A (PKA) prevents inhibition of non-NMDA glutamate receptors by the anticonvulsant topiramate. Using two-electrode voltage-clamp techniques, we demonstrate that PKA activity also modulates topiramate potentiation of recombinant GABA _A receptors expressed in Xenpus laevis oocytes. PKA activators, dibutyryl-cAMP and forskolin, attenuate topiramate potentiation, whereas the PKA inhibitor H-89 increases topiramate potentiation. Thus, endogenous PKA activity and receptor phosphorylation states may contribute to topiramate treatment efficacy.

Original language	English (US)
Pages (from-to)	176-179
Number of pages	4
Journal	Epilepsy Research
Volume	96
Issue number	1-2
DOIs	https://doi.org/10.1016/j.eplepsyres.2011.05.009
State	Published - Sep 2011

All Science Journal Classification (ASJC) codes

Neurology
Clinical Neurology

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10.1016/j.eplepsyres.2011.05.009

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title = "CAMP-Dependent protein kinase A activity modulates topiramate potentiation of GABA A receptors",

abstract = "Activation of cAMP-dependent protein kinase A (PKA) prevents inhibition of non-NMDA glutamate receptors by the anticonvulsant topiramate. Using two-electrode voltage-clamp techniques, we demonstrate that PKA activity also modulates topiramate potentiation of recombinant GABA A receptors expressed in Xenpus laevis oocytes. PKA activators, dibutyryl-cAMP and forskolin, attenuate topiramate potentiation, whereas the PKA inhibitor H-89 increases topiramate potentiation. Thus, endogenous PKA activity and receptor phosphorylation states may contribute to topiramate treatment efficacy.",

author = "Simeone, {Timothy A.} and Wilcox, {Karen S.} and White, {H. Steve}",

note = "Funding Information: The authors would like to sincerely thank Dr. Michael McIntosh and associates for supplying Xenopus laevis oocytes. We also thank Dr. Kristina A. Simeone for critical comments on this manuscript. This work was supported by an unrestricted grant by R.W. Johnson Pharmaceutical Research and Development, Springhouse, PA (HSW) and a Health Future Foundation award (TAS). Copyright: Copyright 2012 Elsevier B.V., All rights reserved.",

year = "2011",

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doi = "10.1016/j.eplepsyres.2011.05.009",

language = "English (US)",

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journal = "Journal of Epilepsy",

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AU - Simeone, Timothy A.

AU - Wilcox, Karen S.

AU - White, H. Steve

N1 - Funding Information: The authors would like to sincerely thank Dr. Michael McIntosh and associates for supplying Xenopus laevis oocytes. We also thank Dr. Kristina A. Simeone for critical comments on this manuscript. This work was supported by an unrestricted grant by R.W. Johnson Pharmaceutical Research and Development, Springhouse, PA (HSW) and a Health Future Foundation award (TAS). Copyright: Copyright 2012 Elsevier B.V., All rights reserved.

PY - 2011/9

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N2 - Activation of cAMP-dependent protein kinase A (PKA) prevents inhibition of non-NMDA glutamate receptors by the anticonvulsant topiramate. Using two-electrode voltage-clamp techniques, we demonstrate that PKA activity also modulates topiramate potentiation of recombinant GABA A receptors expressed in Xenpus laevis oocytes. PKA activators, dibutyryl-cAMP and forskolin, attenuate topiramate potentiation, whereas the PKA inhibitor H-89 increases topiramate potentiation. Thus, endogenous PKA activity and receptor phosphorylation states may contribute to topiramate treatment efficacy.

AB - Activation of cAMP-dependent protein kinase A (PKA) prevents inhibition of non-NMDA glutamate receptors by the anticonvulsant topiramate. Using two-electrode voltage-clamp techniques, we demonstrate that PKA activity also modulates topiramate potentiation of recombinant GABA A receptors expressed in Xenpus laevis oocytes. PKA activators, dibutyryl-cAMP and forskolin, attenuate topiramate potentiation, whereas the PKA inhibitor H-89 increases topiramate potentiation. Thus, endogenous PKA activity and receptor phosphorylation states may contribute to topiramate treatment efficacy.

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CAMP-Dependent protein kinase A activity modulates topiramate potentiation of GABA _A receptors

Abstract

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