Toxoplasma gondii tachyzoites possess an unusual plasma membrane adenosine transporter

J. Conrad Schwab, Mohammed Afifi Afifi, Giuseppe Pizzorno, Robert E. Handschumacher, Keith A. Joiner

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Nucleoside transport may play a critical role in successful intracellular parasitism by Toxoplasma gondii. This protozoan is incapable of de novo purine synthesis, and must salvage purines from the host cell. We characterized purine transport by extracellular T. gondii tachyzoites, focusing on adenosine, the preferred salvage substrate. Although wild-type RH tachyzoites concentrated [3H]adenosine 1.8-fold within 30 s, approx. half of the [3H]adenosine was converted to nucleotide, consistent with the known high parasite adenosine kinase activity. Studies using an adenosine kinase deficient mutant confirmed that adenosine transport was non-concentrative. [14C]Inosine, [14C]hypoxanthine and [3H]adenine transport was also rapid and non-concentrative. Adenosine transport was inhibited by dipyridamole (IC50 approx. 0.7 μM), but not nitrobenzylthioinosine (15 μM). Transport of inosine, hypoxanthine and adenine was minimally inhibited by 10 μM dipyridamole, however. Competition experiments using unlabeled nucleosides and bases demonstrated distinct inhibitor profiles for [3H]adenosine and [14C]inosine transport. These results are most consistent with a single, dipyridamole-sensitive, adenosine transporter located in the T. gondii plasma membrane. Additional permeation pathways for inosine, hypoxanthine, adenine and other purimes may also be present.

Original languageEnglish (US)
Pages (from-to)59-69
Number of pages11
JournalMolecular and Biochemical Parasitology
Volume70
Issue number1-2
DOIs
StatePublished - Mar 1995
Externally publishedYes

Keywords

  • Dipyridamole
  • Nitrobenzylthioinosine
  • Nucleoside transport
  • Protozoan
  • Purine

ASJC Scopus subject areas

  • Parasitology
  • Molecular Biology

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