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. 1991 Oct 1;115(1):179–190. doi: 10.1083/jcb.115.1.179

Coordinate developmental regulation of purine catabolic enzyme expression in gastrointestinal and postimplantation reproductive tracts

PMCID: PMC2289931  PMID: 1918135

Abstract

Using histochemical detection, we have visualized in situ the complete metabolic pathway for the degradation of purine nucleotides. From the tongue to the ileum, diverse epithelial cell types lining the lumen of the mouse gastrointestinal (GI) tract strongly coexpress each of the five key purine catabolic enzymes. Dramatic increases in the expression of each enzyme occurred during postnatal maturation of the GI tract. Using in situ hybridization, an intense accumulation of adenosine deaminase (ADA) mRNA was detected only within GI epithelial cells undergoing postmitotic differentiation. In a similar manner, at the developing maternal-fetal interface, high level expression of the purine catabolic pathway also occurred in a unique subset of maternal decidual cells previously known to express high levels of alkaline phosphatase and ADA. This induction occurred almost immediately after implantation in the periembryonic maternal decidual cells, shortly thereafter in antimesometrial decidual cells, and later in cells of the placental decidua basalis: all of which contain cell types thought to be undergoing programmed cell death. The expression of the pathway at the site of embryo implantation appears to be critical because its pharmacologic inhibition during pregnancy has been found to be embryolethal or teratogenic. Purine destruction at these nutritional interfaces (placenta and gastrointestinal tract) seem to override any potential economy of purine salvage, and may represent biochemical adaptation to nucleic acid breakdown occurring in the context of dietary digestion or extensive programmed cell death.

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Selected References

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  1. Aronow B., Kaur K., McCartan K., Ullman B. Two high affinity nucleoside transporters in Leishmania donovani. Mol Biochem Parasitol. 1987 Jan 2;22(1):29–37. doi: 10.1016/0166-6851(87)90066-1. [DOI] [PubMed] [Google Scholar]
  2. Aronow B., Lattier D., Silbiger R., Dusing M., Hutton J., Jones G., Stock J., McNeish J., Potter S., Witte D. Evidence for a complex regulatory array in the first intron of the human adenosine deaminase gene. Genes Dev. 1989 Sep;3(9):1384–1400. doi: 10.1101/gad.3.9.1384. [DOI] [PubMed] [Google Scholar]
  3. BRADY T. G., O'DONOVAN C. I. A STUDY OF THE TISSUE DISTRIBUTION OF ADENOSINE DEAMINASE IN SIX MAMMAL SPECIES. Comp Biochem Physiol. 1965 Jan;14:101–120. doi: 10.1016/0010-406x(65)90011-3. [DOI] [PubMed] [Google Scholar]
  4. Barton R., Martiniuk F., Hirschhorn R., Goldschneider I. Inverse relationship between adenosine deaminase and purine nucleoside phosphorylase in rat lymphocyte populations. Cell Immunol. 1980 Jan;49(1):208–214. doi: 10.1016/0008-8749(80)90071-4. [DOI] [PubMed] [Google Scholar]
  5. Berlin R. D., Hawkins R. A. Secretion of purines by the small intestine: general characteristics. Am J Physiol. 1968 Oct;215(4):932–941. doi: 10.1152/ajplegacy.1968.215.4.932. [DOI] [PubMed] [Google Scholar]
  6. Chechik B. E., Baumal R., Sengupta S. Localization and identity of adenosine deaminase-positive cells in tissues of the young rat and calf. Histochem J. 1983 Apr;15(4):373–387. doi: 10.1007/BF01002970. [DOI] [PubMed] [Google Scholar]
  7. Chinsky J. M., Ramamurthy V., Fanslow W. C., Ingolia D. E., Blackburn M. R., Shaffer K. T., Higley H. R., Trentin J. J., Rudolph F. B., Knudsen T. B. Developmental expression of adenosine deaminase in the upper alimentary tract of mice. Differentiation. 1990 Feb;42(3):172–183. doi: 10.1111/j.1432-0436.1990.tb00759.x. [DOI] [PubMed] [Google Scholar]
  8. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  9. Dinjens W. N., ten Kate J., Wijnen J. T., van der Linden E. P., Beek C. J., Lenders M. H., Khan P. M., Bosman F. T. Distribution of adenosine deaminase-complexing protein in murine tissues. J Biol Chem. 1989 Nov 15;264(32):19215–19220. [PubMed] [Google Scholar]
  10. Elion G. B. The purine path to chemotherapy. Science. 1989 Apr 7;244(4900):41–47. doi: 10.1126/science.2649979. [DOI] [PubMed] [Google Scholar]
  11. Finn C. A., Martin L. Patterns of cell division in the mouse uterus during early pregnancy. J Endocrinol. 1967 Dec;39(4):593–597. doi: 10.1677/joe.0.0390593. [DOI] [PubMed] [Google Scholar]
  12. Finn C. A. The biology of decidual cells. Adv Reprod Physiol. 1971;5:1–26. [PubMed] [Google Scholar]
  13. Fujii T., Nishimura H. Comparison of teratogenic action of substances related to purine metabolism in mouse embryos. Jpn J Pharmacol. 1972 Apr;22(2):201–206. doi: 10.1254/jjp.22.201. [DOI] [PubMed] [Google Scholar]
  14. GETLER H., ROLL P. M. A study of the metabolism of dietary hypoxanthine and xanthine in the rat. J Biol Chem. 1949 Mar;178(1):259–264. [PubMed] [Google Scholar]
  15. Giblett E. R., Anderson J. E., Cohen F., Pollara B., Meuwissen H. J. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972 Nov 18;2(7786):1067–1069. doi: 10.1016/s0140-6736(72)92345-8. [DOI] [PubMed] [Google Scholar]
  16. Gordon J. I. Intestinal epithelial differentiation: new insights from chimeric and transgenic mice. J Cell Biol. 1989 Apr;108(4):1187–1194. doi: 10.1083/jcb.108.4.1187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hall K. 5-nucleotidase, acid phosphatase and phosphorylase during normal, delayed and induced implantation of blastocysts in mice: a histochemical study. J Endocrinol. 1971 Oct;51(2):291–301. doi: 10.1677/joe.0.0510291. [DOI] [PubMed] [Google Scholar]
  18. Hirschhorn R., Roegner-Maniscalco V., Kuritsky L., Rosen F. S. Bone marrow transplantation only partially restores purine metabolites to normal in adenosine deaminase-deficient patients. J Clin Invest. 1981 Dec;68(6):1387–1393. doi: 10.1172/JCI110389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ho C. Y., Miller K. V., Savaiano D. A., Crane R. T., Ericson K. A., Clifford A. J. Absorption and metabolism of orally administered purines in fed and fasted rats. J Nutr. 1979 Aug;109(8):1377–1382. doi: 10.1093/jn/109.8.1377. [DOI] [PubMed] [Google Scholar]
  20. Katz S., Abrahamsohn P. A. Involution of the antimesometrial decidua in the mouse. An ultrastructural study. Anat Embryol (Berl) 1987;176(2):251–258. doi: 10.1007/BF00310059. [DOI] [PubMed] [Google Scholar]
  21. Knudsen T. B., Blackburn M. R., Chinsky J. M., Airhart M. J., Kellems R. E. Ontogeny of adenosine deaminase in the mouse decidua and placenta: immunolocalization and embryo transfer studies. Biol Reprod. 1991 Jan;44(1):171–184. doi: 10.1095/biolreprod44.1.171. [DOI] [PubMed] [Google Scholar]
  22. Knudsen T. B., Gray M. K., Church J. K., Blackburn M. R., Airhart M. J., Kellems R. E., Skalko R. G. Early postimplantation embryolethality in mice following in utero inhibition of adenosine deaminase with 2'-deoxycoformycin. Teratology. 1989 Dec;40(6):615–626. doi: 10.1002/tera.1420400609. [DOI] [PubMed] [Google Scholar]
  23. Knudsen T. B., Green J. D., Airhart M. J., Higley H. R., Chinsky J. M., Kellems R. E. Developmental expression of adenosine deaminase in placental tissues of the early postimplantation mouse embryo and uterine stroma. Biol Reprod. 1988 Nov;39(4):937–951. doi: 10.1095/biolreprod39.4.937. [DOI] [PubMed] [Google Scholar]
  24. Kulkarni A. D., Fanslow W. C., Drath D. B., Rudolph F. B., Van Buren C. T. Influence of dietary nucleotide restriction on bacterial sepsis and phagocytic cell function in mice. Arch Surg. 1986 Feb;121(2):169–172. doi: 10.1001/archsurg.1986.01400020055006. [DOI] [PubMed] [Google Scholar]
  25. Kulkarni A. D., Fanslow W. C., Rudolph F. B., Van Buren C. T. Effect of dietary nucleotides on response to bacterial infections. JPEN J Parenter Enteral Nutr. 1986 Mar-Apr;10(2):169–171. doi: 10.1177/0148607186010002169. [DOI] [PubMed] [Google Scholar]
  26. Lee P. C. Developmental changes of adenosine deaminase, xanthine oxidase, and uricase in mouse tissues. Dev Biol. 1973 Apr;31(2):227–233. doi: 10.1016/0012-1606(73)90259-5. [DOI] [PubMed] [Google Scholar]
  27. Ma D. D., Sylwestrowicz T. A., Granger S., Massaia M., Franks R., Janossy G., Hoffbrand A. V. Distribution of terminal deoxynucleotidyl transferase and purine degradative and synthetic enzymes in subpopulations of human thymocytes. J Immunol. 1982 Oct;129(4):1430–1435. [PubMed] [Google Scholar]
  28. Nagy J. I., LaBella L. A., Buss M., Daddona P. E. Immunohistochemistry of adenosine deaminase: implications for adenosine neurotransmission. Science. 1984 Apr 13;224(4645):166–168. doi: 10.1126/science.6142530. [DOI] [PubMed] [Google Scholar]
  29. Norstrand I. F. Histochemical demonstration of adenosine deaminase in the human neuraxis. Preliminary observations. Neurochem Pathol. 1985 Summer;3(2):73–82. doi: 10.1007/BF02834281. [DOI] [PubMed] [Google Scholar]
  30. Rundles R. W. The development of allopurinol. Arch Intern Med. 1985 Aug;145(8):1492–1503. [PubMed] [Google Scholar]
  31. Sackler M. L. Xanthine oxidase from liver and duodenum of the rat: histochemical localization and electrophoretic heterogeneity. J Histochem Cytochem. 1966 Apr;14(4):326–333. doi: 10.1177/14.4.326. [DOI] [PubMed] [Google Scholar]
  32. Savaiano D. A., Ho C. Y., Chu V., Clifford A. J. Metabolism of orally and intravenously administered purines in rats. J Nutr. 1980 Sep;110(9):1793–1804. doi: 10.1093/jn/110.9.1793. [DOI] [PubMed] [Google Scholar]
  33. Schrader W. P., West C. A. Localization of adenosine deaminase and adenosine deaminase complexing protein in rabbit heart. Implications for adenosine metabolism. Circ Res. 1990 Mar;66(3):754–762. doi: 10.1161/01.res.66.3.754. [DOI] [PubMed] [Google Scholar]
  34. Semenza G. The J.E. Purkyne lecture: the insertion of stalked proteins of the brush border membranes: the state of the art in 1988. Biochem Int. 1989 Jan;18(1):15–33. [PubMed] [Google Scholar]
  35. Sim M. K., Maguire M. H. Variation in placental adenosine deaminase activity during gestation. Biol Reprod. 1970 Apr;2(2):291–298. doi: 10.1095/biolreprod2.2.291. [DOI] [PubMed] [Google Scholar]
  36. Sonoda T., Tatibana M. Metabolic fate of pyrimidines and purines in dietary nucleic acids ingested by mice. Biochim Biophys Acta. 1978 Nov 21;521(1):55–66. doi: 10.1016/0005-2787(78)90248-4. [DOI] [PubMed] [Google Scholar]
  37. Stewart I., Peel S. The differentiation of the decidua and the distribution of metrial gland cells in the pregnant mouse uterus. Cell Tissue Res. 1978 Feb 14;187(1):167–179. doi: 10.1007/BF00220629. [DOI] [PubMed] [Google Scholar]
  38. Stochaj U., Dieckhoff J., Mollenhauer J., Cramer M., Mannherz H. G. Evidence for the direct interaction of chicken gizzard 5'-nucleotidase with laminin and fibronectin. Biochim Biophys Acta. 1989 Sep 15;992(3):385–392. doi: 10.1016/0304-4165(89)90101-3. [DOI] [PubMed] [Google Scholar]
  39. Van Buren C. T., Kulkarni A. D., Fanslow W. C., Rudolph F. B. Dietary nucleotides, a requirement for helper/inducer T lymphocytes. Transplantation. 1985 Dec;40(6):694–697. doi: 10.1097/00007890-198512000-00024. [DOI] [PubMed] [Google Scholar]
  40. WILSON D. W., WILSON H. C. Studies in vitro of the digestion and absorption of purine ribonucleotides by the intestine. J Biol Chem. 1962 May;237:1643–1647. [PubMed] [Google Scholar]
  41. Welsh A. O., Enders A. C. Light and electron microscopic examination of the mature decidual cells of the rat with emphasis on the antimesometrial decidua and its degeneration. Am J Anat. 1985 Jan;172(1):1–29. doi: 10.1002/aja.1001720102. [DOI] [PubMed] [Google Scholar]
  42. Wiginton D. A., Coleman M. S., Hutton J. J. Purification, characterization and radioimmunoassay of adenosine deaminase from human leukaemic granulocytes. Biochem J. 1981 May 1;195(2):389–397. doi: 10.1042/bj1950389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Williams M. Purine receptors in mammalian tissues: pharmacology and functional significance. Annu Rev Pharmacol Toxicol. 1987;27:315–345. doi: 10.1146/annurev.pa.27.040187.001531. [DOI] [PubMed] [Google Scholar]
  44. Yamamoto T., Geiger J. D., Daddona P. E., Nagy J. I. Subcellular, regional and immunohistochemical localization of adenosine deaminase in various species. Brain Res Bull. 1987 Oct;19(4):473–484. doi: 10.1016/0361-9230(87)90152-3. [DOI] [PubMed] [Google Scholar]
  45. Yeung C. Y., Ingolia D. E., Roth D. B., Shoemaker C., Al-Ubaidi M. R., Yen J. Y., Ching C., Bobonis C., Kaufman R. J., Kellems R. E. Identification of functional murine adenosine deaminase cDNA clones by complementation in Escherichia coli. J Biol Chem. 1985 Aug 25;260(18):10299–10307. [PubMed] [Google Scholar]
  46. van Kreel B. K., van Dijk J. P., Pijnenburg A. M. Placental transfer and metabolism of purines and nucleosides in the pregnant guinea pig. Placenta. 1982 Apr-Jun;3(2):127–136. doi: 10.1016/s0143-4004(82)80046-5. [DOI] [PubMed] [Google Scholar]

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