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.
authors.affiliation: Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT 84112, United States.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Simeone
authors.forename: Karen S
authors.initials: KS
authors.lastname: Wilcox
authors.forename: H Steve
authors.initials: HS
authors.lastname: White
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001703:Biophysics / Q000379:methods; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007814:Larva; D008564:Membrane Potentials / Q000187:drug effects* / Q000235:genetics; D008845:Microinjections / Q000379:methods; D009865:Oocytes; D018408:Patch-Clamp Techniques / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D000077236:Topiramate; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D021122:Protein Subunits; D011963:Receptors, GABA-A; D013449:Sulfonamides; D000077236:Topiramate; D005576:Colforsin; D005632:Fructose; D005680:gamma-Aminobutyric Acid; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide