Inhibition of t-[35S]butylbicyclophosphorothionate binding by convulsant agents in primary cultures of cerebellar neurons
| Autor: | Pomés, Anna, Rodríguez-Farré, Eduard, Suñol, Cristina |
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| Přispěvatelé: | European Commission |
| Rok vydání: | 1993 |
| Předmět: | |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 0165-3806 |
| Popis: | The characteristics of the picrotoxinin binding site present on the γ-aminobutyric acidA (GABAA) receptor were studied in neurons using primary cultures of cerebellar granule cells. The binding properties of these sites in intact cultured cells were compared with those measured in cultured cell membrane preparations. (TBPS) binding was performed in cultured rat cerebellar neurons grown for 13 days. Binding parameters (Kd and Bmax) were similar to those reported in the literature determined using brain membranes. However, equilibrium was reached faster when using intact cultured neurons. Convulsant compounds like picrotoxinin (PTX) and pentylenetetrazol (PTZ) competitively inhibited the binding of TBPS in this in vitro system. Convulsant organochlorine pesticides (γ-hexachlorocyclohexane γ-HCH or lindane and the cyclodienes aldrin, endrin, dieldrin and α-endosulfan) competitively inhibited [35S]TBPS binding in cerebellar neuronal cultures. Inhibitory affinity constant (Ki) values were in the nanomolar range, α-endosulfan and endrin being the most potent inhibitors corresponding to their high toxicity in mammals. Stereospecificity was also shown for HCH isomers, the non-convulsant isomers (α- and σ-HCH) being 15–30 times less potent in inhibiting [35S]TBPS binding than the convulsant γ-HCH, while the β-isomer was inactive. This work was supported by BRIDGE Project No. BIOT-0183-C from the Commission of the European Communities and by CICYT Project No SAL91-0707. |
| Databáze: | OpenAIRE |
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