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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/11806

Title: Potentiation and inhibition of glycine receptors by tutin
Authors: Fuentealba, Jorge
Munoz, Braulio
Yevenes, Gonzalo
Moraga-Cid, Gustavo
Perez, Claudia
Guzman, Leonardo
RIGO, Jean-Michel
Aguayo, Luis
Issue Date: 2011
Publisher: Elsevier
Citation: NEUROPHARMACOLOGY, 60. p. 453-459
Abstract: In the present study we characterized the effects of the South American neurotoxin tutin on recombinant glycine receptors (GlyR) expressed in HEK 293 cells using whole-cell patch-clamp techniques. Tutin induced a concentration-dependent inhibition of α1 and α2 homomeric GlyRs, with IC50s of 35 ± 1 and 15 ± 3 μM, respectively. The co-expression of αβ subunits reduced the potency of tutin, thus increasing the IC50 to 51 ± 4 and 41 ± 8 μM for α1β and α2β GlyRs, respectively. The inhibitory effect of tutin was competitive, independent of membrane potential and reversible suggesting a pore independent site. On the other hand, low tutin concentrations enhanced the current, which was not synergic with Zn2+ or ethanol. A mutation in Lys385 altered ethanol but not tutin sensitivity, suggesting different sites for modulation of α1-containing GlyRs. Our results suggest that tutin affects the GlyR by a mechanism distinct to that of picrotoxin and ethanol, and that the pharmacological profile of tutin exhibits a “Zn-like” behaviour. In conclusion, these results provide information on molecular mechanisms important for understanding the toxic effects of a recently discovered South American neurotoxin.
URI: http://hdl.handle.net/1942/11806
DOI: 10.1016/j.neuropharm.2010.10.023
ISI #: 000287054600032
Category: A1
Type: Journal Contribution
Validation: ecoom, 2012
Appears in Collections: Research publications

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