Williams S G, Fanimo O
Ann Trop Med Parasitol. 1975 Sep;69(3):301-9.
The erythrocytic stages of strains of plasmodia sensitive to chloroquine (CQ) concentrate some three to six times more drug than CQ-resistant strains. A simple, but so far untested hypothesis is that the intracellular pH of drug resistant strains is higher than that for sensitive strains. This would result in a reduced accumulation of any weakly basic drug molecule (e.g. CQ) which is capable of passive diffusion through the cellular membran. The mean intracellular pH of erythrocytes parasitised with either CQ-sensitive or CQ-resistant strains of P. berghei was determined, therefore, from the distribution of 14C-5, 5-dimethyloxazolidine-2,4-dione between intra- and extracellular aqueous phases. The results obtained showed that over the range 6-8--7-2 the intracellular pH is governed directly by the extracellular pH and that the intracellular pH of CQ-sensitive parasites is slightly above that for resistant ones, neither being greatly different from that for uninfected erythrocytes. There was no evidence, therefore, to support, the suggested hypothesis. Elimination of this possibility adds weight to the opinion that changes in drug sensitivity of these plasmodia are the result of changes in the properties of drug-binding sites.
对氯喹（CQ）敏感的疟原虫菌株的红细胞内期积累的药物比耐药菌株多约三到六倍。一个简单但迄今未经检验的假说是，耐药菌株的细胞内pH值高于敏感菌株。这将导致任何能够通过细胞膜进行被动扩散的弱碱性药物分子（如CQ）的积累减少。因此，利用14C-5,5-二甲基恶唑烷-2,4-二酮在细胞内和细胞外水相之间的分布，测定了感染伯氏疟原虫CQ敏感或耐药菌株的红细胞的平均细胞内pH值。获得的结果表明，在6.8-7.2的范围内，细胞内pH值直接受细胞外pH值的控制，CQ敏感寄生虫的细胞内pH值略高于耐药寄生虫，两者与未感染红细胞的细胞内pH值均无显著差异。因此，没有证据支持所提出的假说。排除这种可能性进一步证明了以下观点，即这些疟原虫药物敏感性的变化是药物结合位点性质变化的结果。
