Ionotropic glutamate receptors in lungs and airways - Molecular basis for glutamate toxicity
Ionotropic glutamate receptors in lungs and airways - Molecular basis for glutamate toxicity
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DOI：
10.1165/rcmb.2003-0177oc
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发表时间：
2004-02-01
影响因子：
6.4
通讯作者：
Said, SI
中科院分区：
文献类型：
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作者：
Dickman, KG;Youssef, JG;Said, SI
我们早期发现，离子型谷氨酸受体激动剂N-甲基D-天冬氨酸（NMDA）诱导兴奋毒性肺水肿，内源性激活NMDA受体（NMDAR）可以介导氧化应激引起的肺损伤。在这项研究中，我们寻找证据的NMDAR表达在大鼠肺和肺泡巨噬细胞（AM）细胞系NR 8383，并为可能的调节受体表达的NMDA。使用亚型特异性引物，通过逆转录-聚合酶链反应检测NMDAR 1和4种已知NMDAR 2亚型（A、B、C和D）的mRNA的存在。NMDAR 1在检查的所有肺部区域（外周、肺中部和主干）以及气管和AM中表达。未检测到NMDAR 2A和2B亚型的表达，而NMDAR 2C仅存在于外周和中肺样本中。NMDAR 2D是在肺的外周、气体交换区和肺泡巨噬细胞中表达的优势亚型，并且这种表达在用NMDA处理的肺中上调。Western blot证实NMDAR 1蛋白在所有肺区域和AM中的存在。这些发现提供了谷氨酸在大鼠肺和气道中的兴奋性毒性作用的分子生物学基础，并提出了NMDAR在肺和气道功能中可能的生理作用的问题。
We earlier showed that the ionotropic glutamate receptor agonist N-methyl D-aspartate (NMDA) induces excitotoxic pulmonary edema, and that endogenous activation of NMDA receptors (NMDAR) could mediate lung injury caused by oxidative stress. In this study, we searched for evidence of NMDAR expression in the rat lung and in the alveolar macrophage (AM) cell line NR8383, and for possible regulation of receptor expression by NMDA. The presence of mRNAfor NMDAR 1 and the four known NMDAR 2 subtypes (A, B, C, and D) was examined by reverse transcriptase-polymerase chain reaction using isoform-specific primers. NMDAR 1 was expressed in all lung regions examined (peripheral, midlung, and mainstem), as well as in trachea and the AMs. Expression of NMDAR 2A and 2B subtypes was not detected, whereas NMDAR 2C was present only in peripheral and mid-lung samples. NMDAR 2D was the dominant subtype expressed in the peripheral, gas-exchange zone of lung and in alveolar macrophages, and this expression was upregulated in lungs treated with NMDA. Western blot confirmed the presence of NMDAR 1 protein in all lung regions and in AMs. These findings provide a molecular-biological basis for the excitotoxic actions of glutamate in rat lungs and airways, and raise the question of a possible physiologic role for NMDAR in lung and airway function.