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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1981 Nov;78(11):6940–6943. doi: 10.1073/pnas.78.11.6940

Renin, angiotensins, and angiotensin-converting enzyme in neuroblastoma cells: evidence for intracellular formation of angiotensins.

T Okamura, D L Clemens, T Inagami
PMCID: PMC349168  PMID: 6273896

Abstract

The mechanism of formation of various peptide hormones in neuronal cells in the brain is not clear. The question of whether brain angiotensin II is formed by an extracellular mechanism as in the peripheral system or by an intracellular mechanism can be answered by using cloned cells in culture. We have screened several neuroblastoma cell lines of rat and mouse origin and found at least three cell lines that contain renin (EC 3.4.99.19), angiotensin-converting enzyme (dipeptidyl carboxypeptidase; peptidyldipeptide hydrolase, EC 3.4.15.1), and angiotensins I and II. This finding was interpreted to indicate that in these cells angiotensin formation takes place by an intracellular mechanism, in contrast to the extracellular mechanism well known to occur in plasma. This study also demonstrates the existence of viable and cloned cell lines that produce renin.

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Selected References

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

  1. Augusti-Tocco G., Sato G. Establishment of functional clonal lines of neurons from mouse neuroblastoma. Proc Natl Acad Sci U S A. 1969 Sep;64(1):311–315. doi: 10.1073/pnas.64.1.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bennett J. P., Jr, Snyder S. H. Angiotensin II binding to mammalian brain membranes. J Biol Chem. 1976 Dec 10;251(23):7423–7430. [PubMed] [Google Scholar]
  3. Benuck M., Marks N. Subcellular localization and partial purification of a chloride dependent angiotensin-I converting enzyme from rat brain. J Neurochem. 1978 Apr;30(4):729–734. doi: 10.1111/j.1471-4159.1978.tb10778.x. [DOI] [PubMed] [Google Scholar]
  4. Caldwell P. R., Seegal B. C., Hsu K. C., Das M., Soffer R. L. Angiotensin-converting enzyme: vascular endothelial localization. Science. 1976 Mar 12;191(4231):1050–1051. doi: 10.1126/science.175444. [DOI] [PubMed] [Google Scholar]
  5. Changaris D. G., Severs W. B., Keil L. C. Localization of angiotensin in rat brain. J Histochem Cytochem. 1978 Jul;26(7):593–607. doi: 10.1177/26.7.357644. [DOI] [PubMed] [Google Scholar]
  6. Day R. P., Reid I. A. Renin activity in dog brain: enzymological similarity to cathepsin D. Endocrinology. 1976 Jul;99(1):93–100. doi: 10.1210/endo-99-1-93. [DOI] [PubMed] [Google Scholar]
  7. Depierre D., Roth M. Fluorimetric determination of dipeptidyl carboxypeptidase. (angiotensin-I-converting enzyme). Enzyme. 1975;19(2):65–70. doi: 10.1159/000458975. [DOI] [PubMed] [Google Scholar]
  8. Epstein A. N., Fitzsimons J. T., Rolls B. J. Drinking induced by injection of angiotensin into the rain of the rat. J Physiol. 1970 Sep;210(2):457–474. doi: 10.1113/jphysiol.1970.sp009220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ferrario C. M., Gildenberg P. L., McCubbin J. W. Cardiovascular effects of angiotensin mediated by the central nervous system. Circ Res. 1972 Mar;30(3):257–262. doi: 10.1161/01.res.30.3.257. [DOI] [PubMed] [Google Scholar]
  10. Fischer-Ferraro C., Nahmod V. E., Goldstein D. J., Finkielman S. Angiotensin and renin in rat and dog brain. J Exp Med. 1971 Feb 1;133(2):353–361. doi: 10.1084/jem.133.2.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ganten D., Marquez-Julio A., Granger P., Hayduk K., Karsunky K. P., Boucher R., Genest J. Renin in dog brain. Am J Physiol. 1971 Dec;221(6):1733–1737. doi: 10.1152/ajplegacy.1971.221.6.1733. [DOI] [PubMed] [Google Scholar]
  12. Gocke D. J., Sherwood L. M., Oppenhoff I., Gerten J., Laragh J. H. Measurement of plasma angiotensin II and correlation with renin activity. J Clin Endocrinol Metab. 1968 Nov;28(11):1675–1678. doi: 10.1210/jcem-28-11-1675. [DOI] [PubMed] [Google Scholar]
  13. Gorenstein C., Snyder S. H. Two distinct enkephalinases: solubilization, partial purification and separation from angiotensin converting enzyme. Life Sci. 1979 Dec 10;25(24-25):2065–2070. doi: 10.1016/0024-3205(79)90198-x. [DOI] [PubMed] [Google Scholar]
  14. Haber E., Koerner T., Page L. B., Kliman B., Purnode A. Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal human subjects. J Clin Endocrinol Metab. 1969 Oct;29(10):1349–1355. doi: 10.1210/jcem-29-10-1349. [DOI] [PubMed] [Google Scholar]
  15. Hackenthal E., Hackenthal R., Hilgenfeldt U. Purification and partial characterization of rat brain acid proteinase (isorenin). Biochim Biophys Acta. 1978 Feb 10;522(2):561–573. doi: 10.1016/0005-2744(78)90088-8. [DOI] [PubMed] [Google Scholar]
  16. Hirose S., Yokosawa H., Inagami T. Immunochemical identification of renin in rat brain and distinction from acid proteases. Nature. 1978 Jul 27;274(5669):392–393. doi: 10.1038/274392a0. [DOI] [PubMed] [Google Scholar]
  17. Hirose S., Yokosawa H., Inagami T., Workman R. J. Renin and prorenin in hog brain: ubiquitous distribution and high concentration in the pituitary and pineal. Brain Res. 1980 Jun 9;191(2):489–499. doi: 10.1016/0006-8993(80)91297-4. [DOI] [PubMed] [Google Scholar]
  18. Huwyler T., Felix D. Angiotensin II-sensitive neurons in septal areas of the rat. Brain Res. 1980 Aug 11;195(1):187–195. doi: 10.1016/0006-8993(80)90876-8. [DOI] [PubMed] [Google Scholar]
  19. Matoba T., Murakami K., Inagami T. Rat renin: purification and characterization. Biochim Biophys Acta. 1978 Oct 12;526(2):560–571. doi: 10.1016/0005-2744(78)90146-8. [DOI] [PubMed] [Google Scholar]
  20. Michelakis A. M., Yoshida H., Menzie J., Murakami K., Inagami T. A radioimmunoassay for the direct measurement of renin in mice and its application to submaxillary gland and kidney studies. Endocrinology. 1974 Apr;94(4):1101–1105. doi: 10.1210/endo-94-4-1101. [DOI] [PubMed] [Google Scholar]
  21. Minna J., Nelson P., Peacock J., Glazer D., Nirenberg M. Genes for neuronal properties expressed in neuroblastoma x L cell hybrids. Proc Natl Acad Sci U S A. 1971 Jan;68(1):234–239. doi: 10.1073/pnas.68.1.234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Poth M. M., Heath R. G., Ward M. Angiotensin-converting enzyme in human brain. J Neurochem. 1975 Jul;25(1):83–85. doi: 10.1111/j.1471-4159.1975.tb07698.x. [DOI] [PubMed] [Google Scholar]
  23. Schubert D., Heinemann S., Carlisle W., Tarikas H., Kimes B., Patrick J., Steinbach J. H., Culp W., Brandt B. L. Clonal cell lines from the rat central nervous system. Nature. 1974 May 17;249(454):224–227. doi: 10.1038/249224a0. [DOI] [PubMed] [Google Scholar]
  24. Semple P. F., Macrae W. A., Morton J. J. Angiotensin II in human cerebrospinal fluid may be an immunoassay artifact. Clin Sci (Lond) 1980 Dec;59 (Suppl 6):61s–64s. doi: 10.1042/cs059061s. [DOI] [PubMed] [Google Scholar]
  25. Severs W. B., Daniels-Severs A. E. Effects of angiotensin on the central nervous system. Pharmacol Rev. 1973 Sep;25(3):415–449. [PubMed] [Google Scholar]
  26. Sirett N. E., McLean A. S., Bray J. J., Hubbard J. I. Distribution of angiotensin II receptors in rat brain. Brain Res. 1977 Feb 18;122(2):299–312. doi: 10.1016/0006-8993(77)90296-7. [DOI] [PubMed] [Google Scholar]
  27. Swerts J. P., Perdrisot R., Patey G., De La Baume S., Schwartz J. C. 'Enkephalinase' is distinct from brain 'angiotensin-converting enzyme'. Eur J Pharmacol. 1979 Aug 1;57(2-3):279–281. doi: 10.1016/0014-2999(79)90380-7. [DOI] [PubMed] [Google Scholar]
  28. Tomozawa Y., Sueoka N. In vitro segregation of different cell lines with neuronal and glial properties from a stem cell line of rat neurotumor RT4. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6305–6309. doi: 10.1073/pnas.75.12.6305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wigger H. J., Stalcup S. A. Distribution and development of angiotensin converting enzyme in the fetal and newborn rabbit. An immunofluorescence study. Lab Invest. 1978 May;38(5):581–585. [PubMed] [Google Scholar]
  30. Yang H. Y., Neff N. H. Distribution and properties of angiotensin converting enzyme of rat brain. J Neurochem. 1972 Oct;19(10):2443–2450. doi: 10.1111/j.1471-4159.1972.tb01298.x. [DOI] [PubMed] [Google Scholar]

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