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. 1986 Oct;66(1):166–172.

A canine model of induced purine nucleoside phosphorylase deficiency.

W R Osborne, H J Deeg, S J Slichter
PMCID: PMC1542671  PMID: 3026696

Abstract

Purine nucleoside phosphorylase (NP EC 2.4.2.1) deficiency in man is associated with selective T cell dysfunction and normal B cell immunity. To create an in-vivo model of this immune deficiency, we administered 8-aminoguanosine to dogs. This water soluble nucleoside was rapidly converted by NP to the more potent product inhibitor 8-aminoguanine, which had a Ki of 0.52 microM. The accumulation of inosine and exogenous deoxyguanosine in plasma provided evidence that administration of 8-aminoguanosine was effectively inhibiting NP activity. Four dogs given 8-aminoguanosine and deoxyguanosine concurrently for 5 consecutive days showed mean reductions in peripheral blood lymphocytes of 65 +/- 9% range (55-75%) over the test period. Granulocytes, red blood cells, and plateletes remained within the normal range. Administration of 8-aminoguanosine to dogs provides a model of NP deficiency that will permit studies of the specific control of lymphopoiesis and in-vivo immune function.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agarwal K. C., Agarwal R. P., Stoeckler J. D., Parks R. E., Jr Purine nucleoside phosphorylase. Microheterogeneity and comparison of kinetic behavior of the enzyme from several tissues and species. Biochemistry. 1975 Jan 14;14(1):79–84. doi: 10.1021/bi00672a013. [DOI] [PubMed] [Google Scholar]
  2. Garrett C., Santi D. V. A rapid and sensitive high pressure liquid chromatography assay for deoxyribonucleoside triphosphates in cell extracts. Anal Biochem. 1979 Nov 1;99(2):268–273. doi: 10.1016/s0003-2697(79)80005-6. [DOI] [PubMed] [Google Scholar]
  3. Giblett E. R., Ammann A. J., Wara D. W., Sandman R., Diamond L. K. Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. Lancet. 1975 May 3;1(7914):1010–1013. doi: 10.1016/s0140-6736(75)91950-9. [DOI] [PubMed] [Google Scholar]
  4. HOLMES R. E., ROBINS R. K. PURINE NUCLEOSIDES. IX. THE SYNTHESIS OF 9-BETA-D-RIBOFURANOSYL URIC ACID AND OTHER RELATED 8-SUBSTITUTED PURINE RIBONUCLEOSIDES. J Am Chem Soc. 1965 Apr 20;87:1772–1776. doi: 10.1021/ja01086a028. [DOI] [PubMed] [Google Scholar]
  5. Ives D. H., Durham J. P., Tucker V. S. Rapid determination of nucleoside kinase and nucleotidase activities with tritium-labeled substrates. Anal Biochem. 1969 Apr 4;28(1):192–205. doi: 10.1016/0003-2697(69)90170-5. [DOI] [PubMed] [Google Scholar]
  6. Kazmers I. S., Mitchell B. S., Dadonna P. E., Wotring L. L., Townsend L. B., Kelley W. N. Inhibition of purine nucleoside phosphorylase by 8-aminoguanosine: selective toxicity for T lymphoblasts. Science. 1981 Dec 4;214(4525):1137–1139. doi: 10.1126/science.6795718. [DOI] [PubMed] [Google Scholar]
  7. Osborne W. R., Hammond W. P., Dale D. C. Canine cyclic hematopoiesis is associated with abnormal purine and pyrimidine metabolism. J Clin Invest. 1983 May;71(5):1348–1355. doi: 10.1172/JCI110887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Osborne W. R. Human red cell purine nucleoside phosphorylase. Purification by biospecific affinity chromatography and physical properties. J Biol Chem. 1980 Aug 10;255(15):7089–7092. [PubMed] [Google Scholar]
  9. Osborne W. R., Scott C. R. Purine nucleoside phosphorylase deficiency. Measurement of variant protein in four families with enzyme-deficient members by an enzyme-linked immunosorbent assay. Am J Hum Genet. 1980 Nov;32(6):927–933. [PMC free article] [PubMed] [Google Scholar]
  10. Parks R. E., Jr, Brown P. R., Cheng Y. C., Agarwal K. C., Kong C. M., Agarwal R. P., Parks C. C. Purine metabolism in primitive erythrocytes. Comp Biochem Physiol B. 1973 Jun 15;45(2):355–364. doi: 10.1016/0305-0491(73)90070-9. [DOI] [PubMed] [Google Scholar]
  11. Stoeckler J. D., Cambor C., Kuhns V., Chu S. H., Parks R. E., Jr Inhibitors of purine nucleoside phosphorylase, C(8) and C(5') substitutions. Biochem Pharmacol. 1982 Jan 15;31(2):163–171. doi: 10.1016/0006-2952(82)90206-4. [DOI] [PubMed] [Google Scholar]
  12. WILKINSON G. N. Statistical estimations in enzyme kinetics. Biochem J. 1961 Aug;80:324–332. doi: 10.1042/bj0800324. [DOI] [PMC free article] [PubMed] [Google Scholar]

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