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Cyclosporin A: drug treatment in vivo affects the kinetics of [14C]glucose transport in Hymenolepis microstoma in vitro

Published online by Cambridge University Press:  06 April 2009

J. M. Wastling
Affiliation:
Department of Zoology, Tillydrone Avenue, University of Aberdeen, Aberdeen AB9 2TN, Scotland
L. H. Chappell
Affiliation:
Department of Zoology, Tillydrone Avenue, University of Aberdeen, Aberdeen AB9 2TN, Scotland

Summary

The transport of [14C]glucose by Hymenolepis microstoma in vitro following in vivo treatment with cyclosporin A (CsA) was determined over a range of concentrations. For untreated (control) worms glucose uptake showed saturation kinetics with a small diffusion component. Estimates of the maximum velocity of glucose uptake (Vmax) and the affinity of substrate for the glucose transporter (Kt) revealed that untreated 8-day-old worms had a Vmax twice that of 15-day-old worms and that younger worms had a lower Kt. An inverse relationship was demonstrated between log10 worm weight and the rate of uptake of [14C]glucose, reflecting the relatively greater number of glucose transporters due to the larger surface area: volume ratio of smaller worms. Treatment of H. microstoma with CsA in vivo significantly increased the diffusion component of glucose uptake in vitro. Parasites from drug-treated mice had a significantly lower Vmax for glucose uptake than size-matched controls. The affinity of glucose for its transporter in CsA-treated worms (Kt) was not significantly different from size-matched controls. Both juvenile and adult worms underwent transient depletion in total glycogen content after CsA treatment in vivo. The data confirm that CsA treatment in vivo disrupts the functional integrity of the worm tegument, one facet of which is impaired acquisition of glucose.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1994

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References

REFERENCES

Arme, C. A. (1988). Ontogenetic changes in helminth membrane function. Parasitology 96 (Suppl.), S83104.CrossRefGoogle ScholarPubMed
Borel, J. F. (1982). The history of cyclosporin A and its significance. In Cyclosporin A. Proceedings of an International Conference on Cyclosporin A (ed. White, D. J. G.), pp. 517. Amsterdam1: Elsevier Biomedical Press.Google Scholar
Chappell, L. H. (1988). The interactions between drugs and the parasite surface. Parasitology 96 (Suppl.), S16793.CrossRefGoogle ScholarPubMed
Chappell, L. H., Wastling, J. M.& Hurd, H. (1989). Action of cyclosporin A on the tapeworms Hymenolepis microstoma, H. diminuta and Mesocestoides corti in vivo. Parasitology 98, 291–9.CrossRefGoogle ScholarPubMed
Chappell, L. H.& Wastling, J. M. (1992). Cyclosporin A: antiparasite drug, modulator of the host–parasite relationship and immunosuppressant. Parasitology 105 (Suppl.), S2540.CrossRefGoogle ScholarPubMed
Hofstee, B. H. J. (1956). Graphical analysis of single enzyme systems. Enzymologia 17, 273–8.Google ScholarPubMed
Munro, G. H.& McLaren, D. J. (1990). Schistosoma mansoni: morphology and ultrastructure of adult worms recovered from cyclosporin A-treated mice. Parasitology 100, 1928.CrossRefGoogle ScholarPubMed
Pappas, P. W.& Freeman, B. A. (1975). Sodium-dependent glucose transport in the mouse bile duct tapeworm, Hymenolepis microstoma. Journal of Parasitology 61, 434–9.CrossRefGoogle Scholar
Pappas, P. W.& Read, C. P. (1975). Membrane transport in helminth parasites; a review. Experimental Parasitology 37, 469530.CrossRefGoogle ScholarPubMed
Read, C. P., Rothman, A. H.& Simmons, J. E. (1963). Studies on membrane transport, with special reference to parasite–host integration. Annals of the New York Academy of Sciences 113, 154204.CrossRefGoogle ScholarPubMed
Roberts, L. S. (1980). Development of Hymenolepis diminuta in its definitive host. In Biology of the Tapeworm Hymenolepis diminuta (ed. Arai, H. P), pp. 357423. London: Academic Press.CrossRefGoogle Scholar
Wastling, J. M., MacKenzie, K.& Chappell, L. H. (1992). Effects of cyclosporin A on the morphology and tegumentary ultrastructure of Hymenolepis microstoma in vivo. Parasitology 104, 531–8.CrossRefGoogle ScholarPubMed