McColm A A, Hommel M, Trigg P I
Mol Biochem Parasitol. 1980 Apr;1(2):119-27. doi: 10.1016/0166-6851(80)90006-7.
Normal rhesus monkey erythrocytes were incubated with various membrane-active drugs (for 1 h at 37 degrees C) and after thorough washing, were exposed to infection with Plasmodium knowlesi in an invitro cultivation system. The ability of merozoites to infect with drug-pretreated erythrocytes was assessed both by counting the number of infected cells and by measuring the incorporation of [3H]isoleucine into parasite protein. Marked inhibition of invasion was observed with vinblastine and colchicine, at concentrations greater than 5 x 10(-4) M, respectively. At similar concentrations, cytochalasin B or amantadine had no apparent effect. The addition of 10(-3) M 3',5'-cAMP to the medium during the incubation in the presence of colchicine or vinblastine partially decreased the inhibitory effects. The effects of colchicine and vinblastine on parasite invasion may be correlated with a reversible alteration in erythrocyte conformation (spherocytosis) which occurs at similar drug concentrations to those above and which can be relieved by simultaneous incubation with cAMP. A possible mechanism of action is proposed.
将正常恒河猴红细胞与各种膜活性药物一起孵育(在37℃下孵育1小时),彻底洗涤后,在体外培养系统中使其受到诺氏疟原虫感染。通过计数感染细胞的数量以及测量[3H]异亮氨酸掺入寄生虫蛋白的情况,评估裂殖子感染经药物预处理红细胞的能力。分别在浓度大于5×10⁻⁴ M时,观察到长春碱和秋水仙碱对入侵有明显抑制作用。在相似浓度下,细胞松弛素B或金刚烷胺没有明显作用。在秋水仙碱或长春碱存在的孵育过程中,向培养基中添加10⁻³ M 3',5'-环磷酸腺苷可部分降低抑制作用。秋水仙碱和长春碱对寄生虫入侵的影响可能与红细胞构象的可逆改变(球形红细胞症)相关,这种改变发生在与上述相似的药物浓度下,并且可以通过与环磷酸腺苷同时孵育而缓解。提出了一种可能的作用机制。