Fitch C D, Chevli R, Gonzalez Y
J Pharmacol Exp Ther. 1975 Dec;195(3):389-96.
The response of [14C]chloroquine accumulation to the provision of substrate was evaluated using washed erythrocytes infected with Plasmodium berghei CS (chloroquine-susceptible), with P. berghei CR (chloroquine-resistant), with Plasmodium vinckei CS, with P. vinckei CR, or with a strain of P. berghei spontaneously resistant to chloroquine, Plasmodium berghei yoelii 17X. Erythrocytes infected with chloroquine-resistant parasites had a blunted response, particularly to low glucose concentrations. In the presence of 0.5 mM glucose in one set of experiments, for example, chloroquine accumulation increased by a factor of 8 in erythrocytes infected with P. berghei CS whereas there was no increase in erythrocytes infected with P. berghei CR or with P. berghei yoelii 17X; the difference between P. vinckei CS and P. vinckei CR was less dramatic. In every case except for P. berghei CR, the process of chloroquine accumulation in the presence of 5 mM glucose exhibited a component which became saturated at low concentrations of chloroquine in the medium. For P. berghei CR, plotting steady-state accumulation of chloroquine as a function of the concentration of chloroquine in the medium yielded a sigmoid curve, revealing that higher concentrations of chloroquine (above 100 mM) somehow relieve the blunted response to glucose and suggesting that the variation is in the process of accumulation rather than in substrate utilization.
使用感染了伯氏疟原虫CS株（氯喹敏感株）、伯氏疟原虫CR株（氯喹耐药株）、文氏疟原虫CS株、文氏疟原虫CR株或对氯喹自发耐药的伯氏疟原虫约氏疟原虫17X株的洗涤红细胞，评估了[14C]氯喹积累对底物供应的反应。感染氯喹耐药寄生虫的红细胞反应迟钝，尤其是对低葡萄糖浓度的反应。例如，在一组实验中，当存在0.5 mM葡萄糖时，感染伯氏疟原虫CS株的红细胞中氯喹积累增加了8倍，而感染伯氏疟原虫CR株或伯氏疟原虫约氏疟原虫17X株的红细胞中氯喹积累没有增加；文氏疟原虫CS株和文氏疟原虫CR株之间的差异没有那么显著。除伯氏疟原虫CR株外，在所有情况下，5 mM葡萄糖存在下氯喹积累过程在培养基中氯喹浓度较低时都表现出一个饱和成分。对于伯氏疟原虫CR株，将氯喹的稳态积累量绘制为培养基中氯喹浓度的函数，得到一条S形曲线，这表明较高浓度的氯喹（高于100 mM）以某种方式缓解了对葡萄糖的迟钝反应，并表明这种变化在于积累过程而非底物利用过程。
