HYPOXIA-INDUCED MODIFICATION OF THE N-METHYL-D-ASPARTATE RECEPTOR IN THE BRAIN OF THE NEWBORN PIGLET
HYPOXIA-INDUCED MODIFICATION OF THE N-METHYL-D-ASPARTATE RECEPTOR IN THE BRAIN OF THE NEWBORN PIGLET
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DOI：
10.1016/0304-3940(94)91051-0
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发表时间：
1994-02-14
影响因子：
2.5
通讯作者：
DELIVORIAPAPADOPOULOS, M
中科院分区：
文献类型：
--
作者：
HOFFMAN, DJ;MCGOWAN, JE;DELIVORIAPAPADOPOULOS, M
研究了低氧对新生仔猪脑细胞膜N-甲基-D-天冬氨酸(NMDA)受体/离子通道复合体的影响。实验在2-4日龄新生仔猪上进行，麻醉后进行机械通气。实验组将FiO2降至5~7%，造成低氧性缺氧。对照组在常氧条件下进行机械通气。低氧组的组织缺氧通过降低ATP和磷酸肌酸(PCR)水平(分别比正常氧组低52%和81%)进行生化记录。以[H-3]MK-801结合特性(B-max=受体数目，K-d=解离常数)作为NMDA受体修饰的指标。缺氧组B-max由对照组的1.13+/-0.15 pmol/mg蛋白降至0.68+/-0.23 pmol/mg蛋白(P<；0.01)，K-d值由对照组的9.46+/-1.68 nM降至4.87+/-1.42 nM(P<；0.01)。脑细胞膜功能指标Na+，K+-ATPase活性在低氧时由对照的46.5+/-0.40降至40.5/-2.3MU摩尔无机磷(PI)/mg蛋白/h(P<；0.005)。本研究的结果表明，新生仔猪的缺氧改变了大脑皮层中的NMDA受体，导致受体通道的亲和力增加。低氧诱导的NMDA离子/受体复合体的修饰可能是脑兴奋性毒性的一个潜在机制。
The effect of hypoxia on the N-methyl-D-aspartate (NMDA) receptor/ion channel complex in the brain cell membrane of the newborn piglet was studied. Experiments were conducted on newborn piglets, 2-4 days of age, that were anesthetized and mechanically ventilated. Hypoxic hypoxia was induced in the experimental group by lowering the FiO2 to 5-7%. The control group was ventilated under normoxic conditions. Tissue hypoxia was documented biochemically by decreased levels of ATP and phosphocreatine (PCr) in the hypoxic group (52% and 81% lower than the normoxic group, respectively). [H-3]MK-801 binding characteristics (B-max = number of receptors, K-d = dissociation constant) were used as an index of NMDA receptor modification. In hypoxic brains, B-max decreased from the control level of 1.13 +/- 0.15 pmol/mg protein to 0.68 +/- 0.23 pmol/mg protein (P < 0.01) and the K-d value decreased (reflecting increased affinity) from 9.46 +/- 1.68 nM in the control brains to 4.87 +/- 1.42 nM (P < 0.01) in the hypoxic brains. The Na+,K+-ATPase activity, an index of brain cell membrane function, decreased from a control value of 46.5 +/- 0.4 to 40.5 +/- 2.3 mu mol inorganic phosphate (Pi)/mg protein/h (P < 0.005) during hypoxia. The results of this study indicate that hypoxia in newborn piglets modifies the NMDA receptor in the cerebral cortex, resulting in an increased affinity of the receptor channel. Hypoxia-induced modification of the NMDA ion/receptor complex may be a potential mechanism of cerebral excitotoxicity.