Donaldson J, Hill S J
J Neurochem. 1986 Nov;47(5):1476-82. doi: 10.1111/j.1471-4159.1986.tb00781.x.
The disulphide bond-reducing agent 1,4-dithiothreitol (1 mM) produced a marked potentiation of histamine-stimulated accumulation of [3H]inositol phosphates in lithium-treated slices of guinea-pig cerebellum and cerebral cortex. This was seen as a parallel shift of the concentration-response curve for histamine to lower agonist concentrations, with no significant effect on the maximal response or Hill coefficient. Dithiothreitol similarly potentiated the augmentation of adenosine-stimulated cyclic AMP accumulation elicited by histamine in guinea-pig cerebral cortex. Studies with partial agonists suggested that this potentiating effect was associated with an increase in agonist efficacy rather than a change in agonist binding affinity. Thus, dithiothreitol increased the maximal accumulation of [3H]inositol phosphates produced by both 2-pyridylethylamine and 2-methylhistamine, which appeared to act as partial agonists in guinea-pig cerebral cortex. Dithiothreitol similarly increased the maximal extent of the augmentation of adenosine-stimulated accumulation of cyclic AMP produced by 2-methylhistamine. The site of action of dithiothreitol is not known; however, a comparison of the effect of dithiothreitol on muscarinic and histamine H1-receptor-mediated phosphoinositide responses in guinea-pig cerebral cortex suggests that it is before the stage at which the receptor-effector pathways are shared by these two receptor systems.
二硫键还原剂1,4-二硫苏糖醇（1 mM）显著增强了组胺刺激的豚鼠小脑和大脑皮层锂处理切片中[3H]肌醇磷酸的积累。这表现为组胺浓度-反应曲线平行向较低激动剂浓度偏移，对最大反应或希尔系数无显著影响。二硫苏糖醇同样增强了组胺在豚鼠大脑皮层中引发的腺苷刺激的环磷酸腺苷积累的增强作用。对部分激动剂的研究表明，这种增强作用与激动剂效能的增加有关，而不是激动剂结合亲和力的改变。因此，二硫苏糖醇增加了2-吡啶乙胺和2-甲基组胺产生的[3H]肌醇磷酸的最大积累，这两种物质在豚鼠大脑皮层中似乎作为部分激动剂起作用。二硫苏糖醇同样增加了2-甲基组胺产生的腺苷刺激的环磷酸腺苷积累增强的最大程度。二硫苏糖醇的作用位点尚不清楚；然而，比较二硫苏糖醇对豚鼠大脑皮层毒蕈碱和组胺H1受体介导的磷酸肌醇反应的影响表明，其作用位点在这两个受体系统共享受体-效应器途径之前。
