Leão R M, Gomez M V, Collier B, Prado M A
Departamento de Bioquímica e Imunologia, ICB-UFMG, Belo Horizonte, Brazil.
Brain Res. 1995 Dec 12;703(1-2):86-92. doi: 10.1016/0006-8993(95)01069-6.
In this work, we investigated the effects of two structural analogs of the drug vesamicol, which inhibits the vesicular acetylcholine (ACh) transport, on the potassium-stimulated release of ACh from rat brain cortical slices. These vesamicol analogs, 4-aminobenzovesamicol (ABV) and (trans)-cyclohexovesamicol (transDec), were almost as potent as vesamicol in inhibiting the evoked release of ACh from cortex slices. Similar to vesamicol, the presence of these analogues inhibited the ability of ACh newly-synthesized from [3H]choline to become releasable. However, vesamicol's action was reversible, while ABV and transDec caused a persistent block of this [3H]ACh release. In addition, vesamicol did not affect the release of pre-stored [3H]ACh, but ABV and transDec partially inhibited the release of [3H]ACh in this condition, suggesting that the two latter drugs may alter some of the steps posterior to the entry of [3H]ACh into synaptic vesicles. The rank order of potency for these drugs to reduce ACh release (vesamicol = transDec > ABV) is close to the rank order for inhibition of ACh vesicular transport (transDec > vesamicol > ABV), but is completely different from the order of affinities of these drugs for the vesamicol receptor (ABV > transDec > > vesamicol). These results suggest that although these two vesamicol analogs are able to block ACh release due to their effects on the vesicular transport system, they may have other unexpected actions not shared by vesamicol.
在本研究中，我们考察了药物维西酰胺的两种结构类似物对大鼠脑皮质切片中钾离子刺激的乙酰胆碱（ACh）释放的影响，维西酰胺可抑制囊泡型乙酰胆碱转运。这两种维西酰胺类似物，4-氨基苯维西酰胺（ABV）和（反式）-环己维西酰胺（反式Dec），在抑制皮质切片中诱发的ACh释放方面几乎与维西酰胺一样有效。与维西酰胺相似，这些类似物的存在抑制了由[3H]胆碱新合成的ACh变得可释放的能力。然而，维西酰胺的作用是可逆的，而ABV和反式Dec导致这种[3H]ACh释放的持续阻断。此外，维西酰胺不影响预先储存的[3H]ACh的释放，但ABV和反式Dec在这种情况下部分抑制了[3H]ACh的释放，这表明后两种药物可能改变了[3H]ACh进入突触囊泡后的一些步骤。这些药物降低ACh释放的效力顺序（维西酰胺 = 反式Dec > ABV）接近于抑制ACh囊泡转运的顺序（反式Dec > 维西酰胺 > ABV），但与这些药物对维西酰胺受体的亲和力顺序（ABV > 反式Dec > > 维西酰胺）完全不同。这些结果表明，尽管这两种维西酰胺类似物由于对囊泡转运系统的作用而能够阻断ACh释放，但它们可能具有维西酰胺所没有的其他意外作用。
