Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-17T04:24:52.024Z Has data issue: false hasContentIssue false
  • English
  • Français

Uptake of purine bases and nucleosides in African trypanosomes

Published online by Cambridge University Press:  06 April 2009

Dinah M. James  and
G. V. R. Born
Dinah M. James
Affiliation:
Department of Pharmacology, University of Cambridge, Cambridge CB2 2QD
G. V. R. Born
Affiliation:
Department of Pharmacology, University of Cambridge, Cambridge CB2 2QD
Get access Rights & Permissions [Opens in a new window]

Summary

Uptake of radioactively labelled purine bases and nucleosides by suspensions of Trypanosoma brucei and Trypanosoma congolense in bicine buffer was determined at 37 °C. With T. brucei, the rate of uptake of adenosine was much greater than that of the other compounds tested, the uptake of which decreased in the order adenine, inosine, guanosine and hypoxanthine. With T. brucei, adenosine uptake increased with concentration in a manner suggesting two mechanisms, one with high and the other with low affinity for adenosine. The uptake of adenine increased with concentration only up to about 1·5 µM while the uptake of guanosine increased little with concentration and that of inosine and hypoxanthine not at all. In both species adenosine strongly inhibited the uptake of both of the other nucleosides and of both purine bases. In T. brucei, guanosine and inosine caused small increases in adenosine uptake which was, however, inhibited by them in T. congolense. In T. brucei, each of the purine bases adenine and hypoxanthine inhibited its own uptake maximally but that of each other less effectively. Hypoxanthine was more effective than adenine in inhibiting the uptake of the nucleosides guanosine and inosine, but neither base effected marked inhibition of adenosine uptake. The uptake of adenosine by T. brucei was inhibited by dipyridamole and its analogue, compound RA–233, strongly at 100µM and slightly at 10 µM. The other dipyridamole analogues, VK–744 and VK–774, were ineffective.

Type
Research Article
Information
Parasitology , Volume 81 , Issue 2 , October 1980 , pp. 383 - 393
Copyright
Copyright © Cambridge University Press 1980

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Adams, A. & Harkness, R. A. (1973). Purine uptake from erythrocytes by rabbit tissue in vivo. Biochemical Society Transactions 1, 138–9.CrossRefGoogle Scholar
Born, G. V. R. & Mills, D. C. B. (1969). Potentiation of the inhibitory effect of adenosine on platelet aggregation by drugs that prevent its uptake. Journal of Physiology 202, 41P.Google ScholarPubMed
Gerlach, E., Deuticke, B. & Koss, F. W. (1965). Einfluss von Pyrimidopyrimidin-und Pteridin-Derivaten auf Phosphate-und Adenosin-Permeabilität menschlicher Erythrocyten Arzneimittel-Forschung 15, 558–63.Google Scholar
Guttman, H. C. & Wallace, F. G. (1964). Nutrition and physiology of the Trypanosomatidae. In Biochemistry and Physiology of Protozoa, vol. 3, (ed. Hutner, S. H.), pp. 459–494. New York: Academic Press.Google Scholar
Haslam, R. J. & Rosson, G. M. (1975). Effects of adenosine on levels of adenosine cyclic 3′, 5′-monophosphate in human blood platelets in relation to adenosine incorporation and platelet aggregation. Molecular Pharmacology 11, 528–44.Google ScholarPubMed
Henderson, J. F. & LePage, G. A. (1959). Transport of adenine-8-14C among mouse tissues by blood cells. Journal of Biological Chemistry 234, 3219–23.CrossRefGoogle Scholar
Jaffé, J. J. & Gutteridge, W. E. (1975). Purine and pyrimidine metabolism in protozoa. In Progress in Protozoology, pp. 23–35. 4th International Congress P.U.E.R. Science, Clermont.Google Scholar
Jaffé, J. J., McCormack, J. J. & Meymerian, E. (1970). Trypanocidal properties of 5'-o- Sulfamoyladenosine, a close structural analogue of nucleocidin, Experimental Parasitology 28, 535–43.CrossRefGoogle Scholar
Lanham, S. M. (1968). Separation of trypanosomes from the blood of infected rats and mice by anion-exchangers. Nature, London 218, 1273–4.CrossRefGoogle ScholarPubMed
Liu, M. S. & Feinberg, H. (1971). Incorporation of adenosine-8-14C and inosine-8-14C into rabbit heart adenine nucleotides. American Journal of Physiology 220, 1242–8.CrossRefGoogle ScholarPubMed
Mager, J., Hershko, A., Zeitlin-Beck, R., Shoshani, T. & Razin, A. (1967). Turnover of purine nucleotides in rabbit erythrocytes. Biochimica et biophysica acta 149, 50–8.CrossRefGoogle ScholarPubMed
Miyazaki, H., Nambu, K., Minaki, Y., Hashimoto, M. & Nakamura, K. (1974). The role of direct phosphorylation in the mechanism of adenosine utilisation for nucleotide synthesis in mouse erythrocytes. Journal of Biochemistry 76, 409–17.CrossRefGoogle ScholarPubMed
Philp, R. B., Francey, I. & McElroy, F. (1973). Effect of dipyridamole and five related agents on human platelet aggregation and adenosine uptake. Thrombosis Research 3, 35–50.CrossRefGoogle Scholar
Rubio, R. & Berne, R. M. (1969). Release of adenosine by the normal myocardium in dogs and its relationship to the regulation of coronary resistance. Circulation Research 25, 407–15.CrossRefGoogle Scholar
Sanchez, G., Knight, S. & Strickler, J. (1976). Nucleotide transport in African trypanosomes. Comparative Biochemistry and Physiology 53B, 419–21.Google ScholarPubMed
Sixma, J. J., Lips, J. P. M., Triescnnigg, A. M. C. & Holmsen, H. (1976). Transport and metabolism of adenosine in human blood platelets. Biochimica et biophysica acta 443, 33–48.CrossRefGoogle ScholarPubMed
Taylor, A. E. R., Lanham, S. M. & Williams, J. E. (1974). Influence of methods of pre. paration on the infectivity, agglutination activity and ultrastructure of bloodstream trypanosomes. Experimental Parasitology 35, 196–208.CrossRefGoogle Scholar
Williamson, J. (1970). Review of chemotherapeutic and chemoprophylactic agents. In The African Trypanosomiases, (ed. Mulligan, H. W.), London: Allen and Unwin.Google Scholar
Williamson, J. (1976). Chemotherapy of African trypanosomiasis. Tropical Diseases Bulletin 73, 531–42.Google ScholarPubMed