Potentiation and inhibition of glycine receptors by tutin
| العنوان: | Potentiation and inhibition of glycine receptors by tutin |
|---|---|
| المؤلفون: | Jorge Fuentealba, Gonzalo E. Yévenes, Gustavo Moraga-Cid, Luis G. Aguayo, Jean-Michel Rigo, Braulio Muñoz, Claudia Pérez, Leonardo Guzmán |
| المصدر: | NEUROPHARMACOLOGY Artículos CONICYT CONICYT Chile instacron:CONICYT |
| بيانات النشر: | PERGAMON-ELSEVIER SCIENCE LTD, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Pharmacology, Membrane potential, Dose-Response Relationship, Drug, Plant Extracts, GABAA receptor, Tutin, Tutin, Glycine receptor, Ethanol, Zn2+, GABAA receptor, Picrotoxin, Plant Leaves, Cellular and Molecular Neuroscience, chemistry.chemical_compound, HEK293 Cells, Receptors, Glycine, chemistry, Humans, Picrotoxin, Neurotoxin, Homomeric, Receptor, Sesquiterpenes, Glycine receptor, Protein Binding |
| الوصف: | 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 α(1) and α(2) homomeric GlyRs, with IC(50)s of 35 ± 1 and 15 ± 3 μM, respectively. The co-expression of αβ subunits reduced the potency of tutin, thus increasing the IC(50) to 51 ± 4 and 41 ± 8 μM for α(1)β and α(2)β 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 Zn(2+) 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b4fa5dcaf0233dd2fbb9ea9f1166931Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0b4fa5dcaf0233dd2fbb9ea9f1166931 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |