Bifemelane enhances high K(+)-evoked release of glutamate from mossy fiber synaptosomes of guinea-pig hippocampus.
We have shown that bifemelane augments long-term potentiation in the mossy fiber-CA3 system, but not in the Schaffer collateral-CA1 system. To elucidate the mechanism of action of bifemelane in relation to pathway-specific augmentation of long-term potentiation, we prepared a mossy fiber terminal-rich synaptosomal fraction (P3) from guinea-pig hippocampus and investigated the effect of bifemelane on the release of glutamate from these synaptosomes, using an in vitro superfusion technique. Bifemelane (0.01-1 microM) dose dependently increased the 30 mM K(+)-evoked release of glutamate from the P3 fraction, without affecting glutamate release from a conventional synaptosomal P2 fraction. This stimulatory effect of 1 microM bifemelane was abolished by 100 microM H-7, which also suppressed the increase in K(+)-evoked glutamate release by phorbol 12,13-dibutyrate (1 microM). Bifemelane (1 microM) induced the translocation of protein kinase C activity from cytosol to membrane in the P3 fraction (which contains large and irregular-shaped synaptosomes probably derived from mossy fiber terminals), but not in the P2 fraction. These findings suggest that bifemelane directly acts on mossy fiber terminals to potentiate depolarization-induced glutamate release, which may be at least partly mediated by the translocation (activation) of protein kinase C.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
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Ueda
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Fujii
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Kuraishi
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Satoh
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001665:Binding Sites; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D000928:Antidepressive Agents; D001559:Benzhydryl Compounds; D005971:Glutamates; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D018698:Glutamic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D011188:Potassium; C031906:bifemelane