Terry A V, Silks L A, Dunlap R B, Odom J D, Kosh J W
College of Pharmacy, University of South Carolina, Columbia.
J Pharmacol Exp Ther. 1993 Aug;266(2):593-601.
The pharmacological actions of the novel choline analog, selenonium choline [(CH3)2Se+CH2CH2OH] and its acetyl ester acetylselenonium choline (ASeCh) were studied in vivo and in vitro. ASeCh produced a dose-related decrease in mean arterial pressure in the rat similar to acetylcholine (ACh) but was 1% to 2% as potent. ASeCh demonstrated agonist activity on the rat isolated ileum and was approximately 2% as active as ACh. Selenonium chlorine (SeCh) was taken up and acetylated in brain tissue slices in a time- and concentration-dependent manner. The use of KCl as a loading stimulus did not increase the uptake of SeCh but increased tissue levels of ASeCh 1.5-fold over the control concentrations. The uptake of SeCh was described by a single low-affinity uptake component (Km = 167 microM) that was not blocked by hemicholinium-3. In contrast, hemicholinium significantly blocked the acetylation of SeCh. Compared with basal release, depolarization with KCl caused a significant release of ASeCh into the incubation medium. A neural specificity was suggested for the in vitro uptake of SeCh. Acetylation of SeCh in vivo in the rat after intraventricular administration was similar to the extent of acetylation of [2H4]-choline. ASeCh bound to both M1 and M2 cholinergic receptors with 2% to 3% of the affinity observed for ACh. These data suggest that SeCh may satisfy criteria for a false neurotransmitter precursor.
研究了新型胆碱类似物硒鎓胆碱[（CH3）2Se + CH2CH2OH]及其乙酰酯乙酰硒鎓胆碱（ASeCh）的体内和体外药理作用。ASeCh可使大鼠平均动脉压呈剂量依赖性下降，类似于乙酰胆碱（ACh），但其效力仅为ACh的1%至2%。ASeCh对大鼠离体回肠表现出激动剂活性，活性约为ACh的2%。硒鎓氯胆碱（SeCh）在脑组织切片中被摄取并乙酰化，呈时间和浓度依赖性。使用KCl作为加载刺激并未增加SeCh的摄取，但使ASeCh的组织水平比对照浓度增加了1.5倍。SeCh的摄取由一个单一的低亲和力摄取成分描述（Km = 167 microM），该成分未被半胱氨酸胆碱-3阻断。相比之下，半胱氨酸胆碱显著阻断了SeCh的乙酰化。与基础释放相比，KCl去极化导致ASeCh大量释放到孵育培养基中。提示SeCh的体外摄取具有神经特异性。脑室注射后，大鼠体内SeCh的乙酰化程度与[2H4]-胆碱的乙酰化程度相似。ASeCh与M1和M2胆碱能受体结合，亲和力为ACh的2%至3%。这些数据表明SeCh可能符合假神经递质前体的标准。
