The GABAA antagonist DPP-4-PIOL selectively antagonises tonic over phasic GABAergic currents in dentate gyrus granule cells

Neurochemical Research

Volumn 39, Issue 11, 2014, Pages 2078-2084

  Boddum, Kim ^a   Frølund, Bente ^a   Kristiansen, Uffe ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

4 PIOL derivative; GABAA receptors; Hippocampus; Tonic inhibition

Indexed keywords

3 AMINO 2 (3 CARBOXYPROPYL) 6 (4 METHOXYPHENYL)PYRIDAZINIUM BROMIDE; 4 (3,3 DIPHENYLPROPYL) 5 (4 PIPERDIYL) 3 ISOXAZOLOL HYDROBROMIDE; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 AMINOBUTYRIC ACID A RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG; 4 AMINOBUTYRIC ACID; 5-(4-PIPERIDYL)ISOXAZOL-3-OL; ISOXAZOLE DERIVATIVE; PIPERIDINE DERIVATIVE;

4 AMINOBUTYRIC ACID RELEASE; ARTICLE; BRAIN CELL CULTURE; DENTATE GYRUS; DRUG POTENCY; GRANULE CELL; IC50; WHOLE CELL PATCH CLAMP; XENOPUS; ANIMAL; CELL GRANULE; CHEMISTRY; CYTOLOGY; DRUG EFFECTS; METABOLISM; MOUSE; NERVE CELL;

ANIMALS; CYTOPLASMIC GRANULES; DENTATE GYRUS; GABA-A RECEPTOR ANTAGONISTS; GAMMA-AMINOBUTYRIC ACID; ISOXAZOLES; MICE; NEURONS; PIPERIDINES; RECEPTORS, GABA-A;

EID: 84910122331     PISSN: 03643190     EISSN: 15736903     Source Type: Journal    
DOI: 10.1007/s11064-014-1397-9     Document Type: Article

References (30)

1. Whiting PJ (2003) GABA-A receptor subtypes in the brain: a paradigm for CNS drug discovery? Drug Discov Today 8:445–450. doi:10.1016/S1359-6446(03)02703-X
2. Barnard EA, Skolnick P, Olsen RW et al (1998) International union of pharmacology. XV. Subtypes of gamma-aminobutyric ACIDA receptors: classification on the basis of subunit structure and receptor function. Pharmacol Rev 50:291–314
3. Stell BM, Mody I (2002) Receptors with different affinities mediate phasic and tonic GABA(A) conductances in hippocampal neurons. J Neurosci 22(RC223):2002.
4. Mody I (2001) Distinguishing between GABA(A) receptors responsible for tonic and phasic conductances. Neurochem Res 26:907–913
5. Brickley SG, Cull-Candy SG, Farrant M (1996) Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors. J Physiol 497(Pt 3):753–759
6. Scimemi A, Semyanov A, Sperk G et al (2005) Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus. J Neurosci 25:10016–10024. doi:10.1523/JNEUROSCI.2520-05.2005
7. Nusser Z, Sieghart W, Somogyi P (1998) Segregation of different GABAA receptors to synaptic and extrasynaptic membranes of cerebellar granule cells. J Neurosci 18:1693–1703
8. Stell BM, Brickley SG, Tang CY et al (2003) Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by delta subunit-containing GABAA receptors. Proc Natl Acad Sci USA 100:14439–14444. doi:10.1073/pnas.2435457100
9. Sur C, Quirk K, Dewar D et al (1998) Rat and human hippocampal alpha5 subunit-containing gamma-aminobutyric ACIDA receptors have alpha5beta3gamma2 pharmacological characteristics. Mol Pharmacol 54:928–933. doi:10.1124/mol.54.5.928
10. Saxena NC, Macdonald RL (1996) Properties of putative cerebellar gamma-aminobutyric acid a receptor isoforms. Mol Pharmacol 49:567–579
11. Brown N, Kerby J, Bonnert TP et al (2002) Pharmacological characterization of a novel cell line expressing human alpha(4)beta(3)delta GABA(A) receptors. Br J Pharmacol 136:965–974. doi:10.1038/sj.bjp.0704795
12. Clarkson AN, Huang BS, Macisaac SE et al (2010) Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke. Nature 468:305–309. doi:10.1038/nature09511
13. Sur C, Quirk K, Dewar D et al (1998) Rat and human hippocampal alpha5 subunit-containing gamma-aminobutyric ACIDA receptors have alpha5 beta3 gamma2 pharmacological characteristics. Mol Pharmacol 54:928–933
14. Atack JR, Bayley PJ, Seabrook GR et al (2006) L-655,708 enhances cognition in rats but is not proconvulsant at a dose selective for alpha5-containing GABAA receptors. Neuropharmacology 51:1023–1029. doi:10.1016/j.neuropharm.2006.04.018
15. Pavlov I, Huusko N, Drexel M et al (2011) Progressive loss of phasic, but not tonic, GABAA receptor-mediated inhibition in dentate granule cells in a model of post-traumatic epilepsy in rats. Neuroscience 194:208–219. doi:10.1016/j.neuroscience.2011.07.074
16. Mtchedlishvili Z, Lepsveridze E, Xu H et al (2010) Increase of GABAA receptor-mediated tonic inhibition in dentate granule cells after traumatic brain injury. Neurobiol Dis 38:464–475. doi:10.1016/j.nbd.2010.03.012
17. Frølund B, Jørgensen AT, Tagmose L et al (2002) Novel class of potent 4-arylalkyl substituted 3-isoxazolol GABA(A) antagonists: synthesis, pharmacology, and molecular modeling. J Med Chem 45:2454–2468
18. Krehan D, Storustovu SI, Liljefors T et al (2006) Potent 4-arylalkyl-substituted 3-isothiazolol GABA(A) competitive/noncompetitive antagonists: synthesis and pharmacology. J Med Chem 49:1388–1396. doi:10.1021/jm050987l
19. Glykys J, Mody I (2006) Hippocampal network hyperactivity after selective reduction of tonic inhibition in GABA A receptor alpha5 subunit-deficient mice. J Neurophysiol 95:2796–2807. doi:10.1152/jn.01122.2005
20. Glykys J, Mody I (2007) The main source of ambient GABA responsible for tonic inhibition in the mouse hippocampus. J Physiol 582:1163–1178. doi:10.1113/jphysiol.2007.134460
21. Vardya I, Hoestgaard-Jensen K, Nieto-Gonzalez JL et al (2012) Positive modulation of δ-subunit containing GABA(A) receptors in mouse neurons. Neuropharmacology 63:469–479. doi:10.1016/j.neuropharm.2012.04.023
22. Vestergaard HT, Cannillo C, Frølund B, Kristiansen U (2007) Differences in kinetics of structurally related competitive GABA(A) receptor antagonists. Neuropharmacology 52:873–882. doi:10.1016/j.neuropharm.2006.10.004
23. Mtchedlishvili Z, Kapur J (2006) High-affinity, slowly desensitizing GABAA receptors mediate tonic inhibition in hippocampal dentate granule cells. Mol Pharmacol 69:564–575. doi:10.1124/mol.105.016683
24. Glykys J, Mann EO, Mody I (2008) Which GABA(A) receptor subunits are necessary for tonic inhibition in the hippocampus? J Neurosci 28:1421–1426. doi:10.1523/JNEUROSCI.4751-07.2008
25. Soltesz I, Smetters DK, Mody I (1995) Tonic inhibition originates from synapses close to the soma. Neuron 14:1273–1283
26. Murphy TH, Corbett D (2009) Plasticity during stroke recovery: from synapse to behaviour. Nat Rev Neurosci 10:861–872. doi:10.1038/nrn2735
27. Vardya I, Drasbek KR, Dósa Z, Jensen K (2008) Cell type-specific GABA A receptor-mediated tonic inhibition in mouse neocortex. J Neurophysiol 100:526–532. doi:10.1152/jn.01224.2007
28. Wlodarczyk AI, Sylantyev S, Herd MB et al (2013) GABA-independent GABAA receptor openings maintain tonic currents. J Neurosci 33:3905–3914. doi:10.1523/JNEUROSCI.4193-12.2013
29. Lüddens H, Seeburg PH, Korpi ER (1994) Impact of beta and gamma variants on ligand-binding properties of gamma-aminobutyric acid type A receptors. Mol Pharmacol 45:810–814
30. Ebert B, Thompson SA, Saounatsou K et al (1997) Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol 52:1150–1156