Korolenko T A, Pupyshev A B, Mudrakovskaia A V
Vopr Med Khim. 1987 Sep-Oct;33(5):93-6.
Inhibition of intralysosomal catabolism of proteins was studied in rat liver cells using lysosomotropic drugs suramin (single administration at a dose of 250 mg/kg within 24 and 48 hrs) and chloroquine (at a dose of 30 mg/100 g within 0.5, 1, 3, 6 and 12 hrs after administration). Suramine inhibited pure preparations of cathepsin B and L, while chloroquine inhibited cathepsins B, L and H. The inhibitors were effective in vitro at lower concentrations as compared with these administered in vivo. Less distinct inhibitory effect was observed in the incubation mixture containing an extract of rat liver lysosomes. After administration of the inhibitors in vivo the activity of lysosomal proteinases was not inhibited in rat liver homogenates, which appears to occur due to complex formation between these lysosomotropic drugs and proteins.
使用溶酶体亲和性药物苏拉明(在24小时和48小时内以250毫克/千克的剂量单次给药)和氯喹(给药后0.5、1、3、6和12小时以30毫克/100克的剂量给药),在大鼠肝细胞中研究了对蛋白质溶酶体内分解代谢的抑制作用。苏拉明抑制组织蛋白酶B和L的纯制剂,而氯喹抑制组织蛋白酶B、L和H。与体内给药的浓度相比,这些抑制剂在体外较低浓度时就有效。在含有大鼠肝脏溶酶体提取物的孵育混合物中观察到的抑制作用不太明显。在体内给予抑制剂后,大鼠肝脏匀浆中的溶酶体蛋白酶活性未被抑制,这似乎是由于这些溶酶体亲和性药物与蛋白质之间形成复合物所致。