A putative cytoprotective receptor in the kidney: relation to the neuronal strychnine-sensitive glycine receptor.
A putative cytoprotective receptor in the kidney: relation to the neuronal strychnine-sensitive glycine receptor.
复制标题
肾脏中假定的细胞保护受体：与神经元士的宁敏感的甘氨酸受体的关系。
DOI：
10.1016/0024-3205(94)90078-7
复制
发表时间：
1994
期刊：
影响因子：
6.1
通讯作者：
Schnellmann,RG
中科院分区：
文献类型：
--
作者：
Miller,GW;Schnellmann,RG
中性氨基酸甘氨酸已被证明可以防止暴露于各种毒性损伤的许多细胞类型中的细胞死亡。最近，中枢神经系统（CNS）甘氨酸拮抗剂士的宁被证明特异性结合到肾近端小管（RPT）的质膜和模拟甘氨酸细胞保护。此外，在RPT中已经证明甘氨酸和士的宁在细胞损伤的晚期阻断氯离子流入。本研究的目的是确定RPT细胞保护位点是否与神经元甘氨酸受体相关。只有CNS士的宁敏感性甘氨酸受体的拮抗剂（士的宁，马钱子碱），而不是NMDA受体（DCQX，7-CKA，HA-966）或GABAA受体（bicuculline methiodide，印防己毒素）的甘氨酸调节位点的拮抗剂，阻止线粒体抑制剂（抗霉素A）诱导的RPT细胞死亡。使用免疫印迹分析，在兔肾皮质膜组分和RPT中鉴定了对应于士的宁敏感性甘氨酸受体的58 kDa β-亚基的蛋白质和相关蛋白质桥蛋白。未鉴定出对应于48 kDa α-亚基的蛋白。因此，甘氨酸和士的宁可以通过推定的质膜受体发挥其细胞保护作用，该质膜受体与CNS中发现的士的宁敏感的甘氨酸受体相关。
The neutral amino acid glycine has been demonstrated to prevent cell death in numerous cell types exposed to a variety of toxic insults. Recently, the central nervous system (CNS) glycine antagonist strychine was demonstrated to bind specifically to the plasma membrane of renal proximal tubules (RPT) and mimic glycine cytoprotection. Further, it has been demonstrated in RPT that glycine and strychnine block chloride influx in the late stages of cell injury. The aim of this study was to determine if the RPT cytoprotective site is related to neuronal glycine receptors. Only antagonists tot he CNS strychnine-sensitive glycine receptor (strychnine, brucine), and not antagonists to the glycine modulatory site of the NMDA receptor (DCQX, 7-CKA, HA-966) or the GABAAreceptor (bicuculline methiodide, picrotoxin), prevented mitochondrial inhibitor (antimycin A)-induced RPT cell death. Using immunoblot analysis, proteins corresponding to the 58kDa β-subunit of the strychnine-sensitive glycine receptor and the associated protein gephyrin were identified in rabbit kidney cortical membrane fractions and RPT. No protein corresponding to the 48 kDa α-subunit was identified. Thus, glycine and strychnine may exert their cytoprotective effects via a putative plasma membrane receptor that is related to the strychnine-sensitive glycine receptor found in the CNS.