Nicotine prevents glutamate-induced proteolysis of the microtubule-associated protein MAP-2 and glutamate neurotoxicity in primary cultures of cerebellar neurons.
The aim of this work was to assess whether nicotine prevents glutamate neurotoxicity in primary cultures of cerebellar neurons, to try to identify the receptor mediating the protective effect and to shed light on the step of the neurotoxic process which is prevented by nicotine. It is shown that nicotine prevents glutamate and NMDA neurotoxicity in primary cultures of cerebellar neurons. The protective effect of nicotine is not prevented by atropine, mecamylamine or dihydro-beta-erythroidine, but is slightly prevented by hexamethonium and completely prevented by tubocurarine and alpha-bungarotoxin, indicating that the protective effect is mediated by activation of alpha7 neuronal nicotinic receptors. Moreover, alpha-bungarotoxin potentiates glutamate neurotoxicity, suggesting a tonic prevention of glutamate neurotoxicity by basal activation of nicotinic receptors. Nicotine did not prevent glutamate-induced rise of free intracellular calcium nor depletion of ATP. Nicotine prevents glutamate-induced proteolysis of the microtubule-associated protein MAP-2 and disaggregation of the neuronal microtubular network. The possible mechanism responsible for this prevention is discussed.
Laboratory of Neurobiology, Instituto de Investigaciones Citologicas, Fundación Valenciana de Investigaciones Biomédicas, Spain.
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Miñana
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Montoliu
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Llansola
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Grisolía
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Felipo
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology* / Q000633:toxicity; D018738:Hexamethonium / Q000494:pharmacology; D007700:Kinetics; D008464:Mecamylamine / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology / Q000633:toxicity; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D008869:Microtubule-Associated Proteins; D009498:Neurotoxins; D018733:Nicotinic Antagonists; D014404:Tubulin; D018738:Hexamethonium; D018698:Glutamic Acid; D008464:Mecamylamine; D009538:Nicotine; D002118:Calcium