title: Ligand binding to CNS muscarinic receptor is transiently modified by convulsant 3-mercaptopropionic acid administration.
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.
authors.affiliation: Instituto de Biología Celular y Neurociencias Prof. Eduardo De Robertis, Facultad de Medicina, PROBICENE-CONICET, Universidad de Buenos Aires, Argentina.
authors.forename: P G
authors.initials: PG
authors.lastname: Schneider
authors.forename: G R
authors.initials: GR
authors.lastname: de Lores Arnaiz
mesh_terms: D015097:3-Mercaptopropionic Acid / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008297:Male; D011813:Quinuclidinyl Benzilate / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism; D014316:Tritium
chemical_list: D003292:Convulsants; D008024:Ligands; D011976:Receptors, Muscarinic; D014316:Tritium; D011813:Quinuclidinyl Benzilate; D015097:3-Mercaptopropionic Acid