Nefiracetam modulates acetylcholine receptor currents via two different signal transduction pathways.
Nefiracetam modulates acetylcholine receptor currents via two different signal transduction pathways.
复制标题
奈非拉西坦通过两种不同的信号转导途径调节乙酰胆碱受体电流。
DOI：
10.1124/mol.53.1.1
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发表时间：
1998
影响因子：
3.6
通讯作者：
M. Yoshii
中科院分区：
文献类型：
--
作者：
T. Nishizaki;T. Matsuoka;T. Nomura;K. Sumikawa;T. Shiotani;S. Watabe;M. Yoshii
益智药物被建议作为认知增强剂。然而，潜在的机制在很大程度上是未知的。本研究评估了促脑药奈非西坦介导的天然和突变加利福尼亚雷烟碱乙酰胆碱受体在非洲爪蟾卵母细胞中表达的细胞内信号转导途径。奈非拉西坦在亚微摩尔浓度（0.01 ~ 0.1 μ m）下诱导乙酰胆碱诱发电流短期抑制，在微摩尔浓度（1 ~ 10 μ m）下诱导电流长期增强。抑制是由百日咳毒素敏感、G蛋白调控、camp依赖性蛋白激酶（PKA）的激活引起的，随后乙酰胆碱受体磷酸化；相反，这种增强是由Ca（2+）依赖性蛋白激酶C （PKC）的激活和随后的PKC受体磷酸化引起的。因此，奈非拉西坦与PKA和PKC通路相互作用，这可能解释了认知增强剂作用的细胞机制。
Nootropic agents are proposed to serve as cognition enhancers. The underlying mechanism, however, is largely unknown. The present study was conducted to assess the intracellular signal transduction pathways mediated by the nootropic nefiracetam in the native and mutant Torpedo californica nicotinic acetylcholine (ACh) receptors expressed in Xenopus laevis oocytes. Nefiracetam induced a short-term depression of ACh-evoked currents at submicromolar concentrations (0.01-0.1 microM) and a long-term enhancement of the currents at micromolar concentrations (1-10 microM). The depression was caused by activation of pertussis toxin-sensitive, G protein-regulated, cAMP-dependent protein kinase (PKA) with subsequent phosphorylation of the ACh receptors; in contrast, the enhancement was caused by activation of Ca(2+)-dependent protein kinase C (PKC) and the ensuing PKC phosphorylation of the receptors. Therefore, nefiracetam interacts with PKA and PKC pathways, which may explain a cellular mechanism for the action of cognition-enhancing agents.
影响因子：
56.9
作者：
TANG, CM;SHI, QY;LYNCH, G
通讯作者：
LYNCH, G