Verdier F, Le Bras J, Clavier F, Hatin I, Blayo M C
Antimicrob Agents Chemother. 1985 Apr;27(4):561-4. doi: 10.1128/AAC.27.4.561.
Chloroquine uptake by Plasmodium falciparum-infected human erythrocytes (RBC) was studied in vitro before and during culture by measuring the chloroquine gradient between the cells and medium (C/M) by high-pressure liquid chromatography. The C/M values were 5.9 +/- 2.7 (n = 23) for uninfected RBC, 13 to 34 for six chloroquine-susceptible isolates (concentration required to inhibit 50% of parasite growth, less than 100 nmol/liter) in partially infected RBC (parasitemia from 0.3 to 5%) (n = 28), and 8.4 to 4.9 for four chloroquine-resistant isolates (concentration required to inhibit 50% of parasite growth, 320 to 1,500 nmol/liter) in partially infected RBC (parasitemia from 0.4 to 5%) (n = 26). Two isolates were studied before and after adaptation to continuous culture. C/M was found to decrease (34.2 to 2.1 and 19.3 to 4.9), whereas the concentration required to inhibit 50% of parasite growth increased (35 to 1,400 and 54 to 1,500 nmol/liter), thus indicating the acquisition of chloroquine resistance. These results demonstrate that chloroquine uptake decreased in RBC in which the infective strain, initially susceptible, became resistant in culture and imply that the drug is bound to ferriprotoporphyrin IX to a lesser extent or that a parasite protein competes with ferriprotoporphyrin IX to a greater extent. We suggest that genotypic modifications in the mechanism of chloroquine uptake might occur in the parasite.
通过高压液相色谱法测量细胞与培养基之间的氯喹梯度（C/M），对恶性疟原虫感染的人红细胞（RBC）在体外培养前和培养过程中的氯喹摄取情况进行了研究。未感染红细胞的C/M值为5.9±2.7（n = 23），部分感染红细胞（疟原虫血症为0.3%至5%）中六个氯喹敏感分离株（抑制50%寄生虫生长所需浓度，小于100 nmol/升）的C/M值为13至34（n = 28），部分感染红细胞（疟原虫血症为0.4%至5%）中四个氯喹耐药分离株（抑制50%寄生虫生长所需浓度，320至1500 nmol/升）的C/M值为8.4至4.9（n = 26）。对两个分离株在适应连续培养前后进行了研究。发现C/M降低（34.2至2.1和19.3至4.9），而抑制50%寄生虫生长所需浓度增加（35至1400和54至1500 nmol/升），从而表明获得了氯喹抗性。这些结果表明，在感染菌株最初敏感但在培养中变得耐药的红细胞中，氯喹摄取减少，这意味着药物与铁原卟啉IX的结合程度降低，或者寄生虫蛋白与铁原卟啉IX的竞争程度增加。我们认为，寄生虫在氯喹摄取机制中可能发生了基因型改变。
