Souto-Padrón Thaïs, Lima Ana Paula, Ribeiro Rachel de Oliveira
Instituto de Microbiologia Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Parasitol Res. 2006 Sep;99(4):317-20. doi: 10.1007/s00436-006-0192-1. Epub 2006 Apr 13.
Although local anesthetics (LA) are considered primarily Na+-channel blockers in the past decade, an alternative action of LA as inhibitors of fusion among compartments of the endocytic/exocytic pathways was described. In epimastigote forms of Trypanosoma cruzi, we observed that 50 mM dibucaine reduced the rates of uptake of bovine serum albumin (BSA) and immunoglobulin to 60% of control values in addition to the delay of exocytosis of cysteine proteases. Fusion among endocytic compartments was not inhibited in the presence of dibucaine because previously labeled reservosomes was loaded with a second label in sequential pulse-chase experiments. However, dibucaine reduced the degradation of BSA-gold complex in the reservosomes, which was not caused either by an inhibition of the whole proteolytic activity of the parasite or by a reduction on the expression levels of cruzipain. The immunocytochemical analysis suggested that the inhibition of the degradation of gold-labeled BSA in reservosomes could be due to a subversion of the regular traffic of proteases toward the reservosomes in dibucaine-treated cells.
尽管在过去十年中局部麻醉药（LA）主要被认为是钠离子通道阻滞剂，但也有文献描述了LA作为内吞/外排途径各间隔之间融合抑制剂的另一种作用。在克氏锥虫的前鞭毛体形式中，我们观察到50 mM的丁卡因除了延迟半胱氨酸蛋白酶的胞吐作用外，还将牛血清白蛋白（BSA）和免疫球蛋白的摄取率降低至对照值的60%。在丁卡因存在的情况下，内吞间隔之间的融合并未受到抑制，因为在连续脉冲追踪实验中，先前标记的储存体被加载了第二种标记。然而，丁卡因减少了储存体中BSA-金复合物的降解，这既不是由于寄生虫整体蛋白水解活性的抑制，也不是由于克鲁斯蛋白酶表达水平的降低。免疫细胞化学分析表明，丁卡因处理的细胞中储存体中金标记的BSA降解受到抑制，可能是由于蛋白酶向储存体的正常运输被破坏。
