Chronic ethanol-mediated up-regulation of the N-methyl-D-aspartate receptor polypeptide subunits in mouse cortical neurons in culture
Chronic ethanol-mediated up-regulation of the N-methyl-D-aspartate receptor polypeptide subunits in mouse cortical neurons in culture
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DOI：
10.1074/jbc.271.23.13297
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发表时间：
1996-06-07
影响因子：
4.8
通讯作者：
Ticku, MK
中科院分区：
文献类型：
--
作者：
Follesa, P;Ticku, MK
本研究的目的是确定乙醇介导的 N-甲基-D-天冬氨酸受体 (NMDAR) 的慢性上调是否与哺乳动物皮质神经元中 NMDAR 多肽亚基的增强有关。结果表明，长期乙醇处理导致 R1 和 R2B 多肽亚基增加。 R2A 亚基在这些神经元中不表达。慢性NMDAR拮抗剂（(+)-3-2-(羧基哌嗪-4-基)丙基-1-膦酸(CPP)）治疗也增加了R1和R2B多肽亚基。当乙醇和 CPP 联合使用时，观察到类似的增加。使用非竞争性 NMDAR 拮抗剂 [H-3]MK-801（(+)-5-甲基-10,11-二氢-5H-二苯并[a,d]环苯戊坦-5,10-亚胺马来酸盐）进行的结合研究证实，同时接触乙醇和 CPP 会上调 NMDAR。我们的结果首次证明，长期乙醇处理增加了 NMDA 受体多肽亚基的合成，并且它与 [H-3]MK-801 结合位点的增加有关。
The goal of this study was to determine whether chronic ethanol-mediated up-regulation of the N-methyl-D-aspartate receptors (NMDAR) was associated with an augmentation of the NMDAR polypeptide subunits in the mammalian cortical neurons. The results show that chronic ethanol treatment produced an increase in the R1 and R2B polypeptide subunits. The R2A subunit was not expressed in these neurons. Chronic NMDAR antagonist ((+)-3-2-(carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP)) treatment also increased the R1 and R2B polypeptide subunits. A similar increase was observed when ethanol and CPP were used in combination. Binding studies using [H-3]MK-801 ((+)-5-methyl-10,11-dihydro -5H-dibenzo[a,d]cyclophenptan-5,10-imine maleate), a noncompetitive NMDAR antagonist, confirmed that concomitant exposure of ethanol and CPP up-regulated the NMDAR. Our results demonstrate for the first time that chronic ethanol treatment increased the NMDA receptor polypeptide subunit synthesis and that it was associated with an increase in [H-3]MK-801 binding sites.