日本薬理学雑誌
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
長期増強(LTP)の薬理
創薬における薬理学の役割
佐藤 公道渡辺 繁紀
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ジャーナル フリー

1993 年 102 巻 3 号 p. 225-234

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The physiological characteristics and significance of long-term potentiation in the hippocampus were summarized. In particular, it was pointed out that different mechanisms are involved in the production of hippocampal LTP between the mossy fiber-CA3 system and other systems such as Schaffer collateral-CA1, fimbrial fiber-CA3 and commissural/associational fiber-CA3. Furthermore, the ε-subspecies of protein kinase C (PKC) was demonstrated to be exclusively located at the presynaptic terminals in the hippocampus and activated by arachidonic acid, and this enzyme is suggested to be involved in the production of LTP through a phosphorylation of GAP-43, while the γ-subspecies of PKC may be postsynaptically involved in LTP through an activation of NMDAR1. The production of LTP in the hippocampus is facilitated by many factors such as epidermal growth factor, fibroblast growth factors, somatostatin, M1 receptor agonists and many drugs like anirasetam, bifemelane, idebenone, indeloxazine and vinpocetine, but inhibited by M2-receptor agonists, scopolamine and midazolam. In addition to electrophysiological methods, LTP-like phenomena in 2-deoxyglucose uptake and leucine incorporation can be detected. These LTP phenomena in several animal models will be useful as indices for evaluating facilitatory actions of various compounds on learning/memory functions.
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