Arsenical-resistant trypanosomes lack an unusual adenosine transporter

Nicola S. Carter, Alan H. Fairlamb

Research output: Contribution to journalArticlepeer-review

315 Scopus citations

Abstract

The melaminophenyl arsenical melarsoprol is still used to treat African sleeping sickness a disease caused by parasitic protozoa of the subgroup. Based on the observation that melamine antagonizes the trypanocidal activity of this class of drugs we investigated whether other physiological compounds could compete for the same receptor. Here we report that the trypanolytic effect of melarsen oxide can be specifically abrogated by adenine, adenosine and dipyridamole, all of which compete for uptake by an adenosine transporter. Melarsen-sensitive trypanosomes have two high-affinity adenosine transport systems: a PI type, which also transports inosine; and a P2 type, which also transports adenine and the melaminophenyl arsenicals. Melarsen-resistant trypanosomes lack P2 adenosine transport, suggesting that resistance to these arsenicals is due to loss of uptake.

Original languageEnglish (US)
Pages (from-to)173-176
Number of pages4
JournalNature
Volume361
Issue number6408
DOIs
StatePublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • General

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