A diamidine-resistant Trypanosoma equiperdum clone contains a P2 purine transporter with reduced substrate affinity.

Abstract:

: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.

journal_name

Mol Biochem Parasitol

authors

Barrett MP,Zhang ZQ,Denise H,Giroud C,Baltz T

doi

10.1016/0166-6851(95)00120-p

subject

Has Abstract

pub_date

1995-07-01 00:00:00

pages

223-9

issue

1-2

eissn

0166-6851

issn

1872-9428

pii

0166-6851(95)00120-P

journal_volume

73

pub_type

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