Enhancement of glutamate release by L-fucose changes effects of glutamate receptor antagonists on long-term potentiation in the rat hippocampus.
In previous studies L-fucose has been shown to facilitate long-term memory formation and to enhance and prolong long-term potentiation (LTP). To search for possible presynaptic or postsynaptic mechanisms that are affected by L-fucose, we examined the effect of L-fucose on (1) inhibition of LTP induction via glutamate receptors by antagonists, (2) paired-pulse facilitation, and (3) presynaptic transmitter release. Coapplication of 0.2 mM L-fucose with the competitive N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovalerate (AP5), or coapplication of 0.2 mM L-fucose in the presence of an inhibitor for class I/II metabotropic glutamate receptors, (S)-alpha-methyl-4-carboxyphenylglycine (MCPG), reversed LTP blockade in the CA1-region of hippocampal slices. In contrast, L-fucose had no effect on the LTP blockade by the noncompetitive NMDA ion-channel blocker (5R,10S)-(+)-5-Methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK-801). Paired-pulse facilitation, which is a primarily presynaptic phenomenon of short-term plasticity, was decreased in the presence of 0.2 mM L-fucose. Furthermore, L-fucose enhanced the K(+)-stimulated release of [(3)H]-D-aspartate from preloaded hippocampal slices in a concentration-dependent manner. These observations demonstrate an influence of L-fucose on transmitter release that in turn can increase transmitter availability at postsynaptic glutamate receptors. This effect of L-fucose may contribute to the LTP facilitation seen in vitro and in vivo as well as to improvement in memory formation.
Institute of Pharmacology and Toxicology, Faculty of Medicine, University Otto von Guericke, 39120 Magdeburg, Germany. henry.matthies@medizin.uni-magdeburg.de
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D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000493:pharmacokinetics; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005643:Fucose / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D014316:Tritium
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D005643:Fucose; D001224:Aspartic Acid; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate