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Changes in adenosine transport associated with melaminophenyl arsenical (Mel CY) resistance in Trypanosoma evansi: down-regulation and affinity changes of the P2 transporter

Published online by Cambridge University Press:  05 December 2003

E. A. SUSWAM ,
C. A. ROSS  and
R. J. MARTIN
E. A. SUSWAM
Affiliation:
Center for Tropical Veterinary Medicine, University of Edinburgh, Easter Bush, Roslin, Midlothian EH25 9RG, UK Present address: Department of Neurology, University of Alabama at Birmingham, 1066 THT, 1900 University Boulevard, Birmingham, AL 35294, USA.
C. A. ROSS
Affiliation:
Center for Tropical Veterinary Medicine, University of Edinburgh, Easter Bush, Roslin, Midlothian EH25 9RG, UK
R. J. MARTIN
Affiliation:
Department of Biomedical Sciences, Iowa State University, Ames Iowa, IA 50011, USA
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Abstract

Studies of the kinetics of adenosine transport were carried out on the P1 and P2 transporters of drug-sensitive Trypanosoma evansi and its cloned derivative, resistant to the melaminophenyl arsenical Mel CY. Characterization of adenosine uptake was made by estimation of the maximum concentration taken up at time infinity (Amax). Amax on the P2 transporter of sensitive T. evansi was greater than Amax on the P1 transporter. Amax of the P2 transporter was significantly decreased in drug-resistant trypanosomes. The effect of adenosine concentration and inhibitors, on the rate of adenosine uptake, was described by Michaelis-Menten equations. In sensitive T. evansi, the maximum velocity of adenosine uptake (Vmax) of the P2 transporter was 2-fold greater than Vmax of the P1 transporter. The Vmax of the P2 transporter in resistant parasites was reduced 9-fold. The binding constants Km and Ki on the P2 transporter of resistant T. evansi, showed that resistance was associated with an increased affinity for adenosine, and a decreased affinity for adenine and Berenil. We suggest that resistance to melaminophenyl arsenicals in T. evansi, occurs via 2 mechanisms: (1) a reduction in the number of expressed P2 transporter molecules resulting in decreased uptake of melaminophenyl arsenicals; (2) a change in the binding properties of the P2 transporter.

Keywords

P2 transportersdown-regulationaffinity changesTrypanosoma evansi
Type
Research Article
Information
Parasitology , Volume 127 , Issue 6 , December 2003 , pp. 543 - 549
Copyright
2003 Cambridge University Press

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