Suszkiw J B, Toth G
Brain Res. 1986 Oct 29;386(1-2):371-8. doi: 10.1016/0006-8993(86)90174-5.
A post-stimulation synthesis of acetylcholine (ACh), its incorporation into a 'stable-bound' (vesicular) compartment and subsequent release, were compared in K+-stimulated synaptosomes, in the absence and presence of 10 microM AH5183. The drug depressed by 16% the net intrasynaptosomal formation of ACh from 1 microM [3H]choline (Ch) in the medium, by competitively inhibiting (Ki approximately equal to 20 microM) the high-affinity Ch transport, but it had no direct effect on the intraterminal synthesis of ACh per se. The drug reduced incorporation of newly synthesized [3H]ACh into synaptic vesicles by 55% and subsequent K+-depolarization-induced release of [3H]ACh by 83%, although it had no effect on Ca2+ influx into synaptosomes. These results are consistent with the hypothesis that AH5183 blocks cholinergic neurotransmission presynaptically by interfering with recharging of synaptic vesicles with ACh. Since the reduction of ACh release in the presence of AH5183 had no direct effect on ACh synthesis, these results also suggest that the transmitter release is not prerequisite for enhancement of Ch uptake and ACh synthesis in stimulated nerve terminals.
在有无10微摩尔AH5183存在的情况下，对钾离子刺激的突触体中乙酰胆碱（ACh）的刺激后合成、其掺入“稳定结合”（囊泡）区室以及随后的释放进行了比较。该药物通过竞争性抑制（Ki约等于20微摩尔）高亲和力胆碱转运，使培养基中1微摩尔[3H]胆碱（Ch）的突触体内ACh净形成量降低了16%，但对终末内ACh本身的合成没有直接影响。该药物使新合成的[3H]ACh掺入突触小泡的量减少了55%，随后钾离子去极化诱导的[3H]ACh释放减少了83%，尽管它对钙离子流入突触体没有影响。这些结果与以下假设一致，即AH5183通过干扰用ACh对突触小泡的再填充而在突触前阻断胆碱能神经传递。由于在AH5183存在下ACh释放的减少对ACh合成没有直接影响，这些结果还表明，递质释放不是刺激的神经末梢中胆碱摄取和ACh合成增强的先决条件。
