Fyn-kinase as a determinant of ethanol sensitivity: Relation to NMDA-receptor function
Fyn-kinase as a determinant of ethanol sensitivity: Relation to NMDA-receptor function
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DOI：
10.1126/science.278.5338.698
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发表时间：
1997-10-24
期刊：
影响因子：
56.9
通讯作者：
Niki, H
中科院分区：
文献类型：
--
作者：
Miyakawa, T;Yagi, T;Niki, H
动物对乙醇的敏感性各不相同，这一特性至少部分是由遗传因素决定的。为了确定可能的相关基因，对缺乏Fyn（一种非受体型酪氨酸激酶）的小鼠进行了研究。这些小鼠对乙醇的催眠作用过敏。在对照组小鼠海马中，乙醇可增强n-甲基-d -天冬氨酸受体（NMDAR）的酪氨酸磷酸化，而在fyn缺陷小鼠中则无此作用。对照小鼠对乙醇抑制nmdar介导的海马片兴奋性突触后电位表现出急性耐受性，而fynn缺陷小鼠则没有。这些结果表明Fyn影响对乙醇的行为、生化和生理反应。
Animals vary in their sensitivity to ethanol, a trait at least partly determined by genetic factors. In order to identify possible responsible genes, mice lacking Fyn, a non-receptor type tyrosine kinase, were investigated. These mice were hypersensitive to the hypnotic effect of ethanol. The administration of ethanol enhanced tyrosine phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) in the hippocampus of control mice but not in Fyn-deficient mice. An acute tolerance to ethanol inhibition of NMDAR-mediated excitatory postsynaptic potentials in hippocampal slices developed in control mice but not in Fyn-deficient mice. These results indicate that Fyn affects behavioral, biochemical, and physiological responses to ethanol.