Barrett M P, Zhang Z Q, Denise H, Giroud C, Baltz T
Université de Bordeaux II, URA-CNRS 1637, France.
Mol Biochem Parasitol. 1995 Jul;73(1-2):223-9. doi: 10.1016/0166-6851(95)00120-p.
Following the demonstration that the transport of melaminophenyl arsenical drugs in Trypanosoma brucei is dependent upon an unusual adenosine nucleoside transporter (Carter and Fairlamb, Nature 361 (1993) 173-175) we have investigated adenosine transport in the related parasite Trypanosoma equiperdum (Botat1.1) and a cloned derivative resistant to the diamidine drug berenil (diminazene aceturate) with limited cross-resistance to the melaminophenyl arsenical cymelarsen. The parental strain possesses a bipartite adenosine transport system consisting of one component which is inhibited in a dose-dependent and saturable manner with increasing concentrations of inosine and a second component which is similarly inhibited by adenine. Uptake of adenosine on this second transporter is also inhibited in a dose-dependent fashion by berenil and cymelarsen. Both transporters have high affinity for adenosine (apparent Km values of 0.60 and 0.70 mM and Vmax values of 8.4 and 6.9 pmol (s (10(8) trypanosomes))-1 at 25 degrees C, respectively). Thus T. equiperdum shares with T. brucei a system comprising two adenosine transporters named P1 and P2, respectively. The P1 transporter is similar in the sensitive and resistant T. equiperdum clones, whereas the P2 transporter has reduced transport capacity at physiological adenosine concentration and decreased affinity for adenosine in the drug-resistant clone.
在证明布氏锥虫中三聚氰胺基砷药物的转运依赖于一种不同寻常的腺苷核苷转运体之后（Carter和Fairlamb，《自然》361卷（1993年）173 - 175页），我们研究了相关寄生虫马媾疫锥虫（Botat1.1）以及对双脒药物贝尼尔（二脒那嗪乙酸盐）具有抗性且对三聚氰胺基砷药物赛美拉森具有有限交叉抗性的克隆衍生物中的腺苷转运。亲代菌株拥有一个双组分腺苷转运系统，其中一个组分随着肌苷浓度增加以剂量依赖性和饱和方式受到抑制，另一个组分则同样受到腺嘌呤的抑制。在这个第二个转运体上，腺苷的摄取也受到贝尼尔和赛美拉森的剂量依赖性抑制。两个转运体对腺苷都具有高亲和力（在25℃时，表观Km值分别为0.60和0.70 mM，Vmax值分别为8.4和6.9 pmol·s -1·(108个锥虫)-1）。因此，马媾疫锥虫与布氏锥虫一样，都有一个分别名为P1和P2的双腺苷转运体系统。在敏感和抗性的马媾疫锥虫克隆中，P1转运体相似，而P2转运体在生理腺苷浓度下转运能力降低，并且在耐药克隆中对腺苷的亲和力下降。
