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L-Carnitine increases the affinity of glutamate for quisqualate receptors and prevents glutamate neurotoxicity

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Abstract

We have shown that acute ammonia toxicity is mediated by activation of the NMDA type of glutamate receptors. Although it is well known thatL-carnitine prevents acute ammonia toxicity, the underlying molecular mechanism is not clear. We suspected thatL-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 thatL-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 mML-carnitine, the Ca2+ levels increased only by 50%. Also, AP-3, an antagonist of the metabotropic receptor prevents the protective effect ofL-carnitine against glutamate neurotoxicity. We suggest, therefore, that the protective effect ofL-carnitine against glutamate toxicity is due to the increased affinity of glutamate for the metabotropic receptor. This mechanism could also explain the protection byL-carnitine against acute ammonia toxicity.

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Felipo, V., Miñana, MD., Cabedo, H. et al. L-Carnitine increases the affinity of glutamate for quisqualate receptors and prevents glutamate neurotoxicity. Neurochem Res 19, 373–377 (1994). https://doi.org/10.1007/BF00971588

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