Ligand Binding to CNS Muscarinic Receptor Is Transiently Modified by Convulsant 3-Mercaptopropionic Acid Administration |
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Authors: | Schneider P G de Lores Arnaiz G Rodríguez |
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Institution: | (1) Instituto de Biología Celular y Neurociencias Prof. Eduardo De Robertis, Facultad de Medicina, PROBICENE-CONICET, Universidad de Buenos Aires, Paraguay 2155, 1121 Buenos Aires, Argentina;(2) Instituto de Biología Celular y Neurociencias Prof. Eduardo De Robertis, Facultad de Medicina, PROBICENE-CONICET, Universidad de Buenos Aires, Paraguay 2155, 1121 Buenos Aires, Argentina |
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Abstract: | The administration of convulsant drugs has proven a powerful tool to study experimental epilepsy. We have already reported that the administration of convulsant 3-mercaptopropionic acid (mp) at 150 mg/kg enhances binding affinity of muscarinic antagonist 3H]quinuclidinyl benzilate (3H]QNB) to certain rat CNS membranes during seizure and postseizure without affecting site number. Results obtained with a 100-mg/kg dose of mp have shown reversible increases in 3H]QNB binding to cerebellum and hippocampus, whereas a delayed response has been found in striatum. Neither a subconvulsant dose nor in vitro addition modifies binding. In order to evaluate preseizure, seizure as well as early (30 min) and late (24 h) postseizure stages, we employed a 50 mg/kg dose and tested 3H]QNB binding to CNS membranes. Changes in binding were as follows (in %): in cerebellum, +37, +86, and +40 at preseizure, seizure and early postseizure stages, respectively, but there was a decrease at late postseizure; in hippocampus, +27 at pre- and seizure stages, but a decrease at early and late postseizure. No changes were found in striatum or cerebral cortex membranes at any stage studied. Saturation curves analysed by Scatchard plots indicated that changes in 3H]QNB binding to cerebellar membranes are attributable to an increase in ligand affinity at seizure, followed by a decrease in binding site number at postseizure. A similar profile was observed for hippocampus except that the decrease in binding site number, though lower than at postseizure, was already evident at seizure stage. Results confirm a region-specific response to the convulsant and transient changes provide an example of neuronal plasticity. |
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Keywords: | Muscarinic receptor experimental epilepsy [3H]QNB binding convulsant 3-mercaptopropionic acid seizures neuronal plasticity |
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