ENTRY OF KETOCONAZOLE INTO CANDIDA-ALBICANS
ENTRY OF KETOCONAZOLE INTO CANDIDA-ALBICANS
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DOI：
10.1128/aac.31.2.244
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发表时间：
1987-02-01
影响因子：
4.9
通讯作者：
IMPROVISI, L
中科院分区：
文献类型：
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作者：
BOIRON, P;DROUHET, E;IMPROVISI, L
为了确定酮康唑（KTZ）进入白色念珠菌细胞的特征，我们研究了[3 H]KTZ的摄取。细胞快速且显著地浓缩药物;在不到1分钟内达到最终80倍细胞内浓度的30%，并且在10分钟内达到> 60%。通过简单的扩散机制，在高于0.1875 μ M（0.1 μ g/ml）的细胞外浓度下发生[3 H]KTZ的渗透。在较低浓度下，药物的蓄积是一个主动的、需要能量的过程，至少部分依赖于糖酵解，并且依赖于pH值（最佳pH值为6.6）。主动转运系统具有高结合亲和力（Km = 50 nM）和高最大摄取速度（Vmax = 1.4 μ mol min-1 × 10-7细胞）。不可能用高浓度的未标记KTZ或其他抗真菌剂置换细胞内[3 H]KTZ。这些发现表明，KTZ被迅速吸收，高度浓缩，并与C的细胞成分紧密结合。白色念珠菌
To define characteristics that determine the entry of ketoconazole (KTZ) into Candida albicans cells, we studied the uptake of [3H]KTZ. The cells rapidly and markedly concentrated the drug; 30% of the final 80-fold intracellular concentration was attained in less than 1 min, and > 60% was attained in 10 min. Penetration of [3H]KTZ at an extracellular concentration higher than 0.1875 .mu.M (0.1 .mu.g/ml) occurred by a simple diffusion mechanism. At lower concentrations, accumulation of the drug was an active, energy-requiring process, dependent at least in part on glycolysis, and pH dependent (optimal pH, 6.6). The active transport system had a high binding affinity (Km = 50 nM) and a high maximum velocity of uptake (Vmax = 1.4 .mu.mol min-1 10-7 cells). It was not possible to displace intracellular [3H]KTZ with high concentrations of unlabeled KTZ or other antifungal agents. These findings suggest that KTZ is rapidly taken up, highly concentrated, and tightly bound to cellular components of C. albicans.