Vignes M, Guiramand J, Sassetti I, Recasens M
INSERM U-254 Hôpital St Charles, Montpellier, France.
Neurochem Int. 1992 Sep;21(2):229-35. doi: 10.1016/0197-0186(92)90152-h.
Dithiotreitol (DTT), a sulfhydryl reducing agent inhibits in a dose-dependent manner the inositol phosphates (IPs) accumulation responses evoked by glutamate and potassium without affecting that of carbachol in rat forebrain synaptoneurosomes. Furthermore, DTT neither provokes a depolarization of the membrane, nor increases the internal calcium concentration. Depolarization and internal calcium rise are known to stimulate IPs production. Moreover, DTT does not modify the depolarizing effect and the calcium rise elicited by glutamate and potassium. In addition, the antioxidant compounds 2-aminoethylisothiouronium bromide (AET) and ascorbic acid have no effect on the basal and stimulated IPs accumulation. Thus, it is concluded that: (1) two distinct transduction pathways exist, one stimulated by glutamate and depolarizing agents and the other one by cholinergic agonists; (2) DTT produces its inhibition by reducing disulfide bridges likely at the level of proteins of the phosphoinositide transduction mechanism.
二硫苏糖醇（DTT），一种巯基还原剂，能以剂量依赖的方式抑制谷氨酸和钾诱发的大鼠前脑突触神经小体中肌醇磷酸（IPs）的积累反应，而不影响卡巴胆碱诱发的该反应。此外，DTT既不引起膜去极化，也不增加细胞内钙浓度。已知去极化和细胞内钙升高会刺激IPs的产生。而且，DTT不会改变谷氨酸和钾引起的去极化作用以及钙升高。此外，抗氧化化合物2-氨基乙基异硫脲溴化物（AET）和抗坏血酸对基础的和受刺激的IPs积累没有影响。因此，得出以下结论：（1）存在两种不同的转导途径，一种由谷氨酸和去极化剂刺激，另一种由胆碱能激动剂刺激；（2）DTT可能通过还原磷酸肌醇转导机制中蛋白质水平的二硫键来产生抑制作用。
