Sacaan A I, Johnson K M
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston.
J Pharmacol Exp Ther. 1990 Dec;255(3):1060-3.
The inhibition of N-methyl-D-aspartate (NMDA)-induced [3H]norepinephrine ([3HNE) release by a putrescine analog was studied. We report that arcaine, diguanidinobutane, a putative competitive polyamine antagonist, completely and noncompetitively antagonized NMDA-induced [3H]NE release from rat hippocampal minces with an IC50 value of 102 microM. Arcaine did not alter kainate- or potassium-induced [3H]NE release suggesting a specific effect on NMDA-mediated responses. Spermidine did not alter NMDA-induced [3H]NE release, nor did it reverse the effect of arcaine when introduced in a normal physiologic superfusion buffer. However, spermidine reversed the effect of arcaine when superfusing with buffer that contained 5% (v/v) of the organic solvent dimethylsulfoxide. This finding suggests that the polyamine site may be located at the intracellular surface of the cell membrane. Our results provide the first evidence for polyamine modulation of the NMDA receptor ionophore complex in a functional physiologic system.
研究了一种腐胺类似物对N-甲基-D-天冬氨酸（NMDA）诱导的[3H]去甲肾上腺素（[3HNE]）释放的抑制作用。我们报告称，胍丁胺（一种假定的竞争性多胺拮抗剂）能完全且非竞争性地拮抗NMDA诱导的大鼠海马切片中[3H]NE的释放，其半数抑制浓度（IC50）值为102微摩尔。胍丁胺不会改变红藻氨酸或钾诱导的[3H]NE释放，这表明其对NMDA介导的反应具有特异性作用。亚精胺不会改变NMDA诱导的[3H]NE释放，当在正常生理灌注缓冲液中加入时，它也不会逆转胍丁胺的作用。然而，当用含有5%（v/v）有机溶剂二甲基亚砜的缓冲液进行灌注时，亚精胺会逆转胍丁胺的作用。这一发现表明多胺位点可能位于细胞膜的细胞内表面。我们的结果为功能性生理系统中多胺对NMDA受体离子通道复合物的调节提供了首个证据。
