Eldefrawi M E, Schweizer G, Bakry N M, Valdes J J
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
J Biochem Toxicol. 1988 Spring;3:21-32. doi: 10.1002/jbt.2570030104.
The interaction of diisopropylfluorophosphate (DFP) with the nicotinic acetylcholine (ACh) receptor of Torpedo electric organ was studied, using [3H]-phencyclidine ([3H]-PCP) as a reporter probe. Phencyclidine binds with different kinetics to resting, activated, and desensitized receptor conformations. Although DFP did not inhibit binding of [3H]-ACh or 125I-alpha-bungarotoxin (BGT) to the receptor recognition sites and potentiated in a time-dependent manner [3H]-PCP binding to the receptor's high-affinity allosteric site, it inhibited the ACh- or carbamylcholine-stimulated [3H]-PCP binding. This suggested that DFP bound to a third kind of site on the receptor and affected receptor conformation. Preincubation of the membranes with DFP increased the receptor's affinity for carbamylcholine by eightfold and raised the pseudo-first-order rate of [3H]-PCP binding to that of an agonist-desensitized receptor. Accordingly, it is suggested that DFP induces receptor desensitization by binding to a site that is distinct from the recognition or high-affinity noncompetitive sites.
使用[3H]-苯环己哌啶（[3H]-PCP）作为报告探针，研究了二异丙基氟磷酸酯（DFP）与电鳐电器官烟碱型乙酰胆碱（ACh）受体的相互作用。苯环己哌啶以不同的动力学与静息、激活和脱敏的受体构象结合。尽管DFP不抑制[3H]-ACh或125I-α-银环蛇毒素（BGT）与受体识别位点的结合，并以时间依赖性方式增强[3H]-PCP与受体高亲和力变构位点的结合，但它抑制了ACh或氨甲酰胆碱刺激的[3H]-PCP结合。这表明DFP与受体上的第三种位点结合并影响受体构象。用DFP对膜进行预孵育使受体对氨甲酰胆碱的亲和力提高了八倍，并将[3H]-PCP结合的伪一级速率提高到激动剂脱敏受体的水平。因此，有人认为DFP通过与不同于识别位点或高亲和力非竞争性位点的位点结合来诱导受体脱敏。
