In vitro neuropharmacological evaluation of penitrem-induced tremorgenic syndromes: Importance of the GABAergic system
| Autor: | Angel Moldes-Anaya, Thomas Rundberget, Mattis B. Wigestrand, Frode Fonnum, Gunnar Sundstøl Eriksen, S. Ivar Walaas |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Cerebellum GABAA receptor Glutamate receptor Cell Biology AMPA receptor Mycotoxins Biology Pharmacology Rats Glutamate receptor binding Cellular and Molecular Neuroscience chemistry.chemical_compound medicine.anatomical_structure nervous system chemistry Tremor Penitrem A medicine Animals NMDA receptor GABAergic Rats Wistar gamma-Aminobutyric Acid |
| Zdroj: | Neurochemistry International. 59:1074-1081 |
| ISSN: | 0197-0186 |
| DOI: | 10.1016/j.neuint.2011.08.014 |
| Popis: | The effects of the fungal neurotoxin penitrem A on the GABAergic and glutamatergic systems in rat brain were evaluated. Penitrem A inhibited binding of the GABA A -receptor ligand [ 3 H]TBOB to rat forebrain and cerebellar membrane preparations with IC 50 (half maximal inhibitory concentration) values of 11 and 9 μM, respectively. Furthermore, penitrem A caused a concentration-dependent increase of [ 3 H]flunitrazepam and [ 3 H]muscimol binding in rat forebrain, but not in cerebellar preparations. The stimulation of [ 3 H]flunitrazepam binding by penitrem A was abolished by the addition of GABA. In cerebellar preparations, a different pharmacological profile was found, with penitrem A allosterically inhibiting [ 3 H]TBOB binding by interacting with a bicuculline-sensitive site. Moreover, penitrem A inhibited the high affinity uptake of GABA and glutamate into cerebellar synaptosomes with IC 50 values of 20 and 47 μM, respectively. The toxin showed no effect on NMDA or AMPA glutamate receptor binding. In conclusion, our results suggest that penitrem A exerts region-specific effects in the brain, leading to positive modulation of GABA A -receptor function in forebrain. Conversely, penitrem A may act as a bicuculline-like convulsant in cerebellum. |
| Databáze: | OpenAIRE |
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