title: L-carnitine increases the affinity of glutamate for quisqualate receptors and prevents glutamate neurotoxicity.
abstract: We have shown that acute ammonia toxicity is mediated by activation of the NMDA type of glutamate receptors. Although it is well known that L-carnitine prevents acute ammonia toxicity, the underlying molecular mechanism is not clear. We suspected that L-carnitine would prevent ammonia toxicity by preventing the toxic effects of glutamate. We have tested this hypothesis using primary cultures of neurons. L-carnitine prevented glutamate neurotoxicity in a dose-dependent manner similar to that required to prevent ammonia toxicity in animals. It is also shown that L-carnitine increases selectively the affinity of glutamate for the quisqualate type of glutamate receptors, while the affinity for the kainate and NMDA receptors is slightly decreased. L-carnitine prevents the increase in cytoplasmic Ca2+ induced by addition of glutamate. The Ca2+ levels rose 4.8-fold following addition of 1 mM glutamate, however, when the neurons were incubated previously with 5 mM L-carnitine, the Ca2+ levels increased only by 50%. Also, AP-3, an antagonist of the metabotropic receptor prevents the protective effect of L-carnitine against glutamate neurotoxicity. We suggest, therefore, that the protective effect of L-carnitine against glutamate toxicity is due to the increased affinity of glutamate for the metabotropic receptor. This mechanism could also explain the protection by L-carnitine against acute ammonia toxicity.
authors.affiliation: Instituto de Investigaciones Citológicas de la Fundación Valenciana de Investigaciones Biomédicas, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Felipo
authors.forename: M D
authors.initials: MD
authors.lastname: Miñana
authors.forename: H
authors.initials: H
authors.lastname: Cabedo
authors.forename: S
authors.initials: S
authors.lastname: Grisolía
mesh_terms: D000641:Ammonia / Q000633:toxicity; D000818:Animals; D002331:Carnitine / Q000494:pharmacology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007700:Kinetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism
chemical_list: D000641:Ammonia; D002331:Carnitine; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D018698:Glutamic Acid; D009498:Neurotoxins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate