E Sigel

Summary

Affiliation: University of Bern
Country: Switzerland

Publications

  1. ncbi On the benzodiazepine binding pocket in GABAA receptors
    Dmytro Berezhnoy
    Department of Pharmacology, University of Bern, CH-3010 Bern, Switzerland
    J Biol Chem 279:3160-8. 2004
  2. ncbi Differential cross talk of ROD compounds with the benzodiazepine binding site
    E Sigel
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    Mol Pharmacol 59:1470-7. 2001
  3. ncbi Mapping of the benzodiazepine recognition site on GABA(A) receptors
    Erwin Sigel
    Department of Pharmacology, University of Bern, Bern, Switzerland
    Curr Top Med Chem 2:833-9. 2002
  4. ncbi The Xenopus oocyte: system for the study of functional expression and modulation of proteins
    Erwin Sigel
    Department of Pharmacology, University of Bern, Bern, Switzerland
    Mol Nutr Food Res 49:228-34. 2005
  5. ncbi The benzodiazepine binding pocket of recombinant alpha1beta2gamma2 gamma-aminobutyric acidA receptors: relative orientation of ligands and amino acid side chains
    E Sigel
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    Mol Pharmacol 54:1097-105. 1998
  6. ncbi Electrophysiological evidence for the coexistence of alpha1 and alpha6 subunits in a single functional GABA(A) receptor
    E Sigel
    Department of Pharmacology, University of Bern, Switzerland
    J Neurochem 74:2590-6. 2000
  7. ncbi Point mutations affecting antagonist affinity and agonist dependent gating of GABAA receptor channels
    E Sigel
    Department of Pharmacology, University of Bern, Switzerland
    EMBO J 11:2017-23. 1992
  8. ncbi Allosteric modulation by benzodiazepine receptor ligands of the GABAA receptor channel expressed in Xenopus oocytes
    E Sigel
    Department of Pharmacology, University of Bern, Switzerland
    J Neurosci 8:289-95. 1988
  9. ncbi The antiepileptic drug AWD 131-138 stimulates different recombinant isoforms of the rat GABA(A) receptor through the benzodiazepine binding site
    E Sigel
    Department of Pharmacology, University of Bern, Switzerland
    Neurosci Lett 245:85-8. 1998
  10. ncbi Relative positioning of diazepam in the benzodiazepine-binding-pocket of GABA receptors
    Kelly R Tan
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse, Switzerland
    J Neurochem 111:1264-73. 2009

Collaborators

Detail Information

Publications45

  1. ncbi On the benzodiazepine binding pocket in GABAA receptors
    Dmytro Berezhnoy
    Department of Pharmacology, University of Bern, CH-3010 Bern, Switzerland
    J Biol Chem 279:3160-8. 2004
    ..We present in addition evidence that gamma(2)Ala-79 is probably located in the access pathway of the ligand to its binding pocket...
  2. ncbi Differential cross talk of ROD compounds with the benzodiazepine binding site
    E Sigel
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    Mol Pharmacol 59:1470-7. 2001
    ..ROD178B is a competitive antagonist at the R1 site in that it shows allosteric interaction with the benzodiazepine binding site and displacement of benzodiazepines, and a negative allosteric modulator at the R2 site...
  3. ncbi Mapping of the benzodiazepine recognition site on GABA(A) receptors
    Erwin Sigel
    Department of Pharmacology, University of Bern, Bern, Switzerland
    Curr Top Med Chem 2:833-9. 2002
    ....
  4. ncbi The Xenopus oocyte: system for the study of functional expression and modulation of proteins
    Erwin Sigel
    Department of Pharmacology, University of Bern, Bern, Switzerland
    Mol Nutr Food Res 49:228-34. 2005
  5. ncbi The benzodiazepine binding pocket of recombinant alpha1beta2gamma2 gamma-aminobutyric acidA receptors: relative orientation of ligands and amino acid side chains
    E Sigel
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    Mol Pharmacol 54:1097-105. 1998
    ..Electrophysiological data obtained with the wild-type receptor furthermore suggest a simple overlap between positive allosteric modulators acting at the benzodiazepine binding site with its antagonists...
  6. ncbi Electrophysiological evidence for the coexistence of alpha1 and alpha6 subunits in a single functional GABA(A) receptor
    E Sigel
    Department of Pharmacology, University of Bern, Switzerland
    J Neurochem 74:2590-6. 2000
    ....
  7. ncbi Point mutations affecting antagonist affinity and agonist dependent gating of GABAA receptor channels
    E Sigel
    Department of Pharmacology, University of Bern, Switzerland
    EMBO J 11:2017-23. 1992
    ....
  8. ncbi Allosteric modulation by benzodiazepine receptor ligands of the GABAA receptor channel expressed in Xenopus oocytes
    E Sigel
    Department of Pharmacology, University of Bern, Switzerland
    J Neurosci 8:289-95. 1988
    ..All the tested carboline compounds and Ro 15-1788 showed a biphasic action and stimulated GABA current at concentrations higher than 1 microM.(ABSTRACT TRUNCATED AT 250 WORDS)..
  9. ncbi The antiepileptic drug AWD 131-138 stimulates different recombinant isoforms of the rat GABA(A) receptor through the benzodiazepine binding site
    E Sigel
    Department of Pharmacology, University of Bern, Switzerland
    Neurosci Lett 245:85-8. 1998
    ..3-1.0 microM. One micrometer of the benzodiazepine antagonist flumazenil (Ro 15-1788) counteracted the current stimulation by 10 microM AWD 131-138, indicating that this drug acts at the binding site for benzodiazepines...
  10. ncbi Relative positioning of diazepam in the benzodiazepine-binding-pocket of GABA receptors
    Kelly R Tan
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse, Switzerland
    J Neurochem 111:1264-73. 2009
    ..Based on these observations we propose a relative positioning of diazepam within the benzodiazepine-binding site of alpha(1)beta(2)gamma(2) receptors...
  11. ncbi The rat beta 1-subunit of the GABAA receptor forms a picrotoxin-sensitive anion channel open in the absence of GABA
    E Sigel
    Institute of Pharmacology, University of Bern, Switzerland
    FEBS Lett 257:377-9. 1989
    ..Since this channel could be shunt by the GABA-channel blocker picrotoxin, we conclude that the beta 1-subunit of the GABAA receptor is sufficient to form binding sites for picrotoxin...
  12. ncbi Covalent modification of GABAA receptor isoforms by a diazepam analogue provides evidence for a novel benzodiazepine binding site that prevents modulation by these drugs
    Roland Baur
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    J Neurochem 106:2353-63. 2008
    ..Our results indicate that this site may be located at the alpha/beta subunit interface pseudo-symmetrically to the site for classical benzodiazepines located at the alpha/gamma interface...
  13. ncbi Impact of subunit positioning on GABAA receptor function
    E Sigel
    Department of Biochemistry and Molecular Medicine, University of Bern, CH 3012 Bern, Switzerland
    Biochem Soc Trans 34:868-71. 2006
    ..Similar approaches may be used to characterize other members of the pentameric ligand-gated ion channel family, including nicotinic acetylcholine receptors, glycine receptors and 5-HT3 (5-hydroxytryptamine) receptors...
  14. ncbi Two novel residues in M2 of the gamma-aminobutyric acid type A receptor affecting gating by GABA and picrotoxin affinity
    A Buhr
    Department of Pharmacology, University of Bern, CH-3010 Bern, Switzerland
    J Biol Chem 276:7775-81. 2001
    ..The point mutation in the neighboring residue beta(3)A252V resulted in receptors that displayed an about 6-fold increased apparent affinity to GABA and an about 10-fold reduced sensitivity to picrotoxin...
  15. ncbi On high- and low-affinity agonist sites in GABAA receptors
    Roland Baur
    Department of Pharmacology, University of Bern, Bern, Switzerland
    J Neurochem 87:325-32. 2003
    ..Our observations are relevant for the relative location of high- and low-affinity agonist sites in GABAA receptors...
  16. ncbi A GABA(A) receptor of defined subunit composition and positioning: concatenation of five subunits
    Roland Baur
    Department of Pharmacology, University of Bern, , CH-3010 Bern, Switzerland
    FEBS Lett 580:1616-20. 2006
    ..The ability to express receptors consisting of five subunits enables detailed studies of GABA(A) receptor subtype selective compounds...
  17. ncbi Proximity-accelerated chemical coupling reaction in the benzodiazepine-binding site of gamma-aminobutyric acid type A receptors: superposition of different allosteric modulators
    Kelly R Tan
    Institute of Biochemistry and Molecular Medicine, University of Bern, Buhlstrasse 28, Bern CH 3012, Switzerland
    J Biol Chem 282:26316-25. 2007
    ..Taken together with previous data, a similar orientation of these ligands within the benzodiazepine-binding pocket may be proposed...
  18. ncbi Two neighboring residues of loop A of the alpha1 subunit point towards the benzodiazepine binding site of GABAA receptors
    Kelly R Tan
    Institute of Biochemistry and Molecular Medicine, University of Bern, Buhlstrasse 28, CH 3012 Bern, Switzerland
    FEBS Lett 581:4718-22. 2007
    ..We describe a direct interaction of alpha(1)N102 with a diazepam- and an imidazobenzodiazepine-derivative. Our observations help to better understand the conformation of this region of the benzodiazepine pocket in GABA(A) receptor...
  19. ncbi Individual properties of the two functional agonist sites in GABA(A) receptors
    Sabine W Baumann
    Department of Pharmacology, University of Bern, CH-3010 Bern, Switzerland
    J Neurosci 23:11158-66. 2003
    ....
  20. ncbi Unanticipated structural and functional properties of delta-subunit-containing GABAA receptors
    Kuldeep H Kaur
    Institute of Biochemistry and Molecular Medicine, University of Bern, CH 3012 Bern, Switzerland
    J Biol Chem 284:7889-96. 2009
    ..Furthermore, we show that the delta-subunit can contribute to the formation of an agonist site in alpha(1)-beta(3)-alpha(1)/beta(3)-delta receptors...
  21. ncbi Functional characterization of the new human GABA(A) receptor mutation beta3(R192H)
    Andreas Buhr
    Department of Pharmacology, University of Bern, Friedbuehlstrasse 49, CH 3010 Bern, Switzerland
    Hum Genet 111:154-60. 2002
    ..The mutation beta3(R192H) might, therefore, be linked to this condition. The intron/exon boundaries of the alpha1 subunit gene were also established and three additional variants were found in the alpha1 and beta3 genes...
  22. ncbi The cannabinoid CB1 receptor antagonists rimonabant (SR141716) and AM251 directly potentiate GABA(A) receptors
    R Baur
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstr, Bern, Switzerland
    Br J Pharmacol 165:2479-84. 2012
    ..Concentrations of 0.5-10 µM are usually applied in in vitro experiments. We intended to show that these drugs did not act at GABA(A) receptors but found a significant positive allosteric modulation instead...
  23. ncbi Subunit arrangement of gamma-aminobutyric acid type A receptors
    S W Baumann
    Department of Pharmacology, University of Bern, , CH-3010 Bern, Switzerland
    J Biol Chem 276:36275-80. 2001
    ..Our findings also favor an arrangement betaalphagammabetaalpha for the receptor composed of alpha, beta, and gamma subunits...
  24. ncbi Novel chloride channel mutations leading to mild myotonia among Chinese
    Jean Marc Burgunder
    Division of Neurology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
    Neuromuscul Disord 18:633-40. 2008
    ..Our data suggest that myotonia congenita caused by CLCN1 mutations in Chinese have similar variable features to those found in the West...
  25. ncbi Anticipating antiport in P-type ATPases
    Verena Niggli
    Institute of Pathology, University of Bern, Murtenstrasse 31, Bern, Switzerland
    Trends Biochem Sci 33:156-60. 2008
    ..New data based on the crystal structure of SERCA now strongly indicate that countertransport could be mandatory for all P-type ATPases. This concept should be verified for other known and for all newly characterized P-type ATPases...
  26. ncbi Use of concatamers to study GABAA receptor architecture and function: application to delta-subunit-containing receptors and possible pitfalls
    Erwin Sigel
    Institute of Biochemistry and Molecular Medicine, University of Bern, CH 3012 Bern, Switzerland
    Biochem Soc Trans 37:1338-42. 2009
    ..As some concatenated constructs result by themselves in a low level of expression, this erroneous assembly leading to receptor function may be promoted by overloading the expression system and leads to wrong conclusions...
  27. ncbi Diversity of structure and function of alpha1alpha6beta3delta GABAA receptors: comparison with alpha1beta3delta and alpha6beta3delta receptors
    Roland Baur
    Institute of Biochemistry and Molecular Medicine, University of Bern, CH 3012 Bern, Switzerland
    J Biol Chem 285:17398-405. 2010
    ..This property is shared by alpha(1)beta(3)delta and alpha(6)beta(3)delta receptors, but there are differences in the additionally expressed isoforms...
  28. ncbi Influence of the point mutation alpha-1-H101R on the assembly of gamma-aminobutyric acid type A receptors
    Roland Baur
    Department of Pharmacology, University of Bern, Bern, Switzerland
    Neuroreport 16:1955-8. 2005
    ..Here, we investigated the assembly properties of mutated in comparison with wild-type subunits, and demonstrate that alpha1H101R has similar assembly properties as wild-type alpha1...
  29. ncbi Conformational changes at benzodiazepine binding sites of GABA(A) receptors detected with a novel technique
    Dmytro Berezhnoy
    Department of Pharmacology, University of Bern, Bern, Switzerland
    J Neurochem 92:859-66. 2005
    ..It is concluded that Ro15-1788 efficiently protects activated and desensitized states, but not the resting state...
  30. ncbi Benzodiazepines affect channel opening of GABA A receptors induced by either agonist binding site
    Roland Baur
    Department of Pharmacology, Friedbuehlstrasse 49, CH-3010 Bern, Switzerland
    Mol Pharmacol 67:1005-8. 2005
    ..Both of the receptors harboring only one active agonist site could be stimulated by diazepam. We therefore present evidence that binding of diazepam can affect channel opening induced by either agonist binding site...
  31. ncbi Structure of alpha6 beta3 delta GABA(A) receptors and their lack of ethanol sensitivity
    Roland Baur
    Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
    J Neurochem 111:1172-81. 2009
    ..We conclude from the investigated receptors that the delta subunit can assume multiple positions in a receptor pentamer composed of alpha(6), beta(3) and delta subunits...
  32. ncbi Interaction between GABA(A) receptor beta subunits and the multifunctional protein gC1q-R
    M T Schaerer
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    J Biol Chem 276:26597-604. 2001
    ..Our observations therefore suggest a tight interaction between gC1q-R and the GABA(A) receptor which might be involved in receptor biosynthesis or modulation of the mature function...
  33. ncbi Positioning of the alpha-subunit isoforms confers a functional signature to gamma-aminobutyric acid type A receptors
    Frédéric Minier
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    Proc Natl Acad Sci U S A 101:7769-74. 2004
    ..This method may also be applied to the study of other ion channels...
  34. ncbi Consequence of the presence of two different beta subunit isoforms in a GABA(A) receptor
    Nathalie Boulineau
    Department of Pharmacology, University of Bern, Bern, Switzerland
    J Neurochem 95:1724-31. 2005
    ....
  35. ncbi Monepantel allosterically activates DEG-3/DES-2 channels of the gastrointestinal nematode Haemonchus contortus
    Lucien Rufener
    Institute of Cell Biology, University of Bern, Buhlstrasse 28, CH 3012 Bern, Switzerland
    Mol Pharmacol 78:895-902. 2010
    ..contortus DEG-3/DES-2 receptors with choline. In summary, we present the first direct evidence for interaction of AADs with DEG-3-type acetylcholine receptors and discuss these findings in the context of anthelmintic action of AADs...
  36. ncbi Novel plant substances acting as beta subunit isoform-selective positive allosteric modulators of GABAA receptors
    Roland Baur
    Department of Pharmacology, University of Bern, CH-3010 Bern, Switzerland
    Mol Pharmacol 68:787-92. 2005
    ..In summary, these positive allosteric modulators of GABAA receptors of plant origin have a novel unusual chemical structure and act at a site independent of that of benzodiazepines and loreclezole...
  37. ncbi Techniques: Use of concatenated subunits for the study of ligand-gated ion channels
    Frédéric Minier
    Department of Pharmacology, University of Bern, Friedbühlstr 49, CH 3010 Bern, Switzerland
    Trends Pharmacol Sci 25:499-503. 2004
    ..Thus, this method also facilitates the investigation of positional effects of mutations associated with diseases...
  38. ncbi Function of the alpha 1 beta 2 gamma 2S gamma-aminobutyric acid type A receptor is modulated by protein kinase C via multiple phosphorylation sites
    S Kellenberger
    Department of Pharmacology, University of Bern, Switzerland
    J Biol Chem 267:25660-3. 1992
    ..Co-expression of the mutant subunits suggests that phosphorylation of both sites is required for a full, PKC-mediated down-regulation of GABA currents...
  39. ncbi Forced subunit assembly in alpha1beta2gamma2 GABAA receptors. Insight into the absolute arrangement
    Sabine W Baumann
    Department of Pharmacology, University of Bern, CH-3010 Bern, Switzerland
    J Biol Chem 277:46020-5. 2002
    ..The methods established here should be applicable to the entire ion channel family comprising nicotinic acetylcholine, glycine, and 5HT(3) receptors...
  40. ncbi The flavone hispidulin, a benzodiazepine receptor ligand with positive allosteric properties, traverses the blood-brain barrier and exhibits anticonvulsive effects
    Dominique Kavvadias
    Food Chemistry, University of Wurzburg, Wurzburg D 97074, Germany
    Br J Pharmacol 142:811-20. 2004
    ..At a concentration of 30 microm, the flavone crossed the monolayer without degradation as verified by the absence of glucuronidated metabolites...
  41. ncbi N-Substituted 4-amino-3,3-dipropyl-2(3H)-furanones: new positive allosteric modulators of the GABA(A) receptor sharing electrophysiological properties with the anticonvulsant loreclezole
    Ahmed El Hadri
    Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, 91198 Gif-sur-Yvette Cedex, France
    J Med Chem 45:2824-31. 2002
    ..g., 9a, 9c), and interestingly also alpha-EMTBL, share stimulatory properties with loreclezole...
  42. ncbi Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi
    Kwok Min Hui
    Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
    Biochem Pharmacol 64:1415-24. 2002
    ..Its anxiolytic effect was not accompanied by sedative and myorelaxant side-effects typical of BDZs...
  43. ncbi Naturally occurring 2'-hydroxyl-substituted flavonoids as high-affinity benzodiazepine site ligands
    Michael S Y Huen
    Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
    Biochem Pharmacol 66:2397-407. 2003
    ..These results further underlined the potential of flavonoids as therapeutics for the treatment of BDZR-associated syndromes...
  44. ncbi Exon 17 skipping in CLCN1 leads to recessive myotonia congenita
    Lie Chen
    Departments of Neurology and Clinical Research, Laboratory of Neuromorphology, University of Berne, Berne, Switzerland
    Muscle Nerve 29:670-6. 2004
    ..Our data suggest an important role of this C-terminal region and that exon 17 skipping resulting from a homozygous point mutation in CLCN1 can lead to recessive myotonia congenita...
  45. ncbi The promiscuous role of the epsilon subunit in GABAA receptor biogenesis
    Karen A Bollan
    Neurosciences Institute, Ninewells Medical School, University of Dundee, Dundee DD1 9SY, UK
    Mol Cell Neurosci 37:610-21. 2008
    ..In both cases, it appears that only a single GABA binding site is present...