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The mode of action of suramin on the filarial worm Brugia pahangi

Published online by Cambridge University Press:  06 April 2009

R. E. Howells ,
A. M. Mendis  and
P. G. Bray
R. E. Howells
Affiliation:
Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA
A. M. Mendis
Affiliation:
Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA
P. G. Bray
Affiliation:
Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA
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Summary

The mode of action of suramin upon Brugia pahangi has been investigated in vivo and in vitro. The drug was without effect on the glycolytic activity of worms in vitro at 2 × 10−4 M. The lack of effect was correlated with the failure of [14C]suramin to penetrate the worms in vitro. Suramin bound to the surface of worms in vitro presumably by virtue of its polyanionic nature. B. pahangi adults ingested [14C]suramin in vivo but no reduction in the rate of lactate production, of glucose utilization or in the rates of uptake of [14C]glucose, [14C]leucine or [14C]adenosine was observed in worms recovered from jirds between weeks 1 and 5 following 4 daily doses of suramin at 50 mg/kg given intraperitoneally. Worm death occurred between weeks 5 and 7 but this delayed drug effect was not the result of a progressive accumulation of suramin in the worms. Ultrastructural changes were observed in the intestinal epithelium of worms from suramin-treated jirds and parallel observations on worms exposed to Trypan blue in vivo suggest that both polyanionic compounds are restricted to the intestinal lumen of the worms. The evidence presented is consistent with the concept that, in B. pahangi, suramin acts at the surface of the intestinal epithelium and not by primarily inhibiting glucose catabolism or inhibiting phagosome and lysosome fusion as previously demonstrated for bloodstream trypanosomes and mammalian macrophages, respectively

Type
Research Article
Information
Parasitology , Volume 87 , Issue 1 , August 1983 , pp. 29 - 48
Copyright
Copyright © Cambridge University Press 1983

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