Grimwood S, Struthers L, Foster A C
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Eur J Pharmacol. 1994 Jan 1;266(1):43-50. doi: 10.1016/0922-4106(94)90207-0.
The N-methyl-D-aspartate (NMDA) receptor complex possesses distinct recognition sites for glutamate, glycine and polyamines, which appear to be allosterically linked. We have investigated the effects of polyamines on the binding of the glycine site antagonist 3H-4-(trans)-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino - 1,2,3,4-tetrahydroquinoline ([3H]L-689,560), using rat cortex/hippocampus P2 membranes. Spermine and spermidine partially inhibited [3H]L-689,560 binding under non-equilibrium conditions, with IC50 values of 25.9 and 106 microM, respectively. The putative polyamine site antagonists arcaine, 1,10-diaminodecane, diethylenetriamine and putrescine had no effect on [3H]L-689,560 binding per se at 1 mM. The inhibition of [3H]L-689,560 binding by spermine was antagonised by arcaine in a competitive manner, but not by 1,10-diaminodecane, diethylenetriamine or putrescine. Kinetic analysis revealed that spermine (100 microM) decreased the association and dissociation rates of [3H]L-689,560 binding. In saturation experiments 100 microM spermine increased the KD for [3H]L-689,560 binding from 1.99 nM to 4.03 nM, with no effect on the number of binding sites. Spermine increased the affinity of glycine site agonists in displacing [3H]L-689,560 binding, with no effect on inhibition by partial agonists or antagonists, suggesting that spermine promotes an 'agonist-preferring' state. Modulation of [3H]L-689,560 binding by agonists for the polyamine and glutamate sites on the NMDA receptor did not appear to be additive in nature.
N-甲基-D-天冬氨酸（NMDA）受体复合物具有针对谷氨酸、甘氨酸和多胺的不同识别位点，这些位点似乎通过变构相互联系。我们使用大鼠皮质/海马P2膜，研究了多胺对甘氨酸位点拮抗剂3H-4-(反式)-2-羧基-5,7-二氯-4-苯基氨基羰基氨基-1,2,3,4-四氢喹啉（[3H]L-689,560）结合的影响。在非平衡条件下，精胺和亚金融胺部分抑制[3H]L-689,560的结合，IC50值分别为金融25.9和106微摩尔。假定的多胺位点金融拮抗剂胍丁胺、1,10-二氨基癸烷、二乙烯三胺和金融腐胺在1毫摩尔时对[3H]L-金融金融60金融560结合本身没有影响。精胺对[3H]L-689,560结合的抑制被胍丁胺以竞争方式拮抗，但不被1,10-二氨基癸烷、二金融金融烯金融三胺或腐胺拮抗。动力学分析表明，精胺（100微摩尔）降低了[3H]L-689,560结合金融缔合和解离速率。在饱和实验中，100微摩尔精胺将[3H]L-689,560结合的KD从1.99纳摩尔增加到4.03纳摩尔，对金融金融位点数量没有影响。精胺增加了甘氨酸位点激动剂取代[3H]L-689,5金融0结合金融亲和力，对部分激动剂或拮抗剂的抑制没有影响，这表明精金融促进了一种“激动剂偏好”状态。NMDA受体金融多胺和谷氨酸位点激动剂对[金融]L-689,560结合金融调节在本质上似乎金融加和性的。
