Inositol trisphosphate receptor localization in brain: variable stoichiometry with protein kinase C (original) (raw)

Nature volume 325, pages 159–161 (1987)Cite this article

Abstract

Many neurotransmitters, hormones and growth factors act at membrane receptors to stimulate the phosphodiesteratic hydrolysis of phosphatidyl-inositol 4,5-bisphosphate generating the co-messengers inositol 1,4,5-trisphosphate (Ins(l,4,5)P3) and diacylglycerol1,2. Diacylglycerol stimulates protein kinase C3 while Ins(l,4,5)P3 is postulated to activate specific receptors leading to release of intracellular calcium4–9, probably from the endoplasmic reticulum10. In recent preliminary reports, Rubin and associates11–13 detected 32P-Ins(l,4,5)P3 binding to liver and adrenal microsomes and to permeabilized neutrophils and liver cells. We now report the biochemical and autoradiographic demonstration in brain of high affinity, selective binding sites for 3H- and 32P-labelled Ins(l,4,5)P3 at levels 100–300 times higher than those observed in peripheral tissues. The potencies of various myo-inositol analogues at the Ins(l,4,5)P3 binding site correspond to their potencies in releasing calcium from microsomes1, supporting the physiological relevance of this receptor. Brain autoradiograms demonstrate discrete, heterogeneous localizations of Ins(l,4,5)P3 receptors. In some regions localizations of Ins(l,4,5)P3 receptors resemble those of protein kinase C14, while in others they differ markedly, suggesting a novel mechanism whereby the relative activity of the two limbs of the PI cycle can be differently regulated

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References

  1. Berridge, M. J. & Irvine, R. F. Nature 312, 315–321 (1984).
    Article ADS CAS Google Scholar
  2. Downes, C. P. & Michell, R. H. Cell Calcium 3, 467–502 (1982).
    Article CAS Google Scholar
  3. Nishizuka, Y. Nature 308, 693–698 (1984).
    Article ADS CAS Google Scholar
  4. Streb, H., Irvine, R. F., Berridge, M. J. & Shulz, I. Nature 306, 67–68 (1983).
    Article ADS CAS Google Scholar
  5. Burgess, G. M. et al. Nature 309, 63–66 (1984).
    Article ADS CAS Google Scholar
  6. Suematsu, E., Hirata, M., Hashimoto, T. & Kuriyama, H. Biochem. biophys. Res. Commun. 120, 481–485 (1984).
    Article CAS Google Scholar
  7. Prentki, M. et al. Nature 309, 562–564 (1984).
    Article ADS CAS Google Scholar
  8. Streb, H., Bayerdorffer, E., Haase, W., Irvine, R. F. & Schulz, I. J. Membrane Biol. 81, 241–253 (1984).
    Article CAS Google Scholar
  9. Dawson, A. P. & Irvine, R. F. Biochem. biophys. Res. Commun. 120, 858–864 (1984).
    Article CAS Google Scholar
  10. Burgess, G. M., Irvine, R. F., Berridge, M. J., McKinney, J. S. & Putney, J. W. Jr Biochem. J. 224, 741–746 (1984).
    Article CAS Google Scholar
  11. Baukal, A. J., Guillemette, G., Rubin, R., Spat, A. & Catt, K. J. Biochem. biophys. Res. Commun. 133, 532–538 (1985).
    Article CAS Google Scholar
  12. Spat, A., Fabiato, A. & Rubin, R. P. Biochem. J. 233, 929–932 (1986).
    Article CAS Google Scholar
  13. Spat, A., Bradford, P. G., McKinney, J. S., Rubin, R. P. & Putney, J. W. Jr Nature 319, 514–516 (1986).
    Article ADS CAS Google Scholar
  14. Worley, P. F., Baraban, J. M. & Snyder, S. H. J. Neurosci. 6, 199–207 (1986).
    Article CAS Google Scholar
  15. Downes, C. P. & Michell, R. H. Biochem. J. 198, 133–140 (1981).
    Article CAS Google Scholar
  16. Erneux, C., Delvaux, A., Moreau, C. & Dumont, J. E. Biochem. biophys. Res. Commun. 134, 351–358 (1986).
    Article CAS Google Scholar
  17. Irvine, R. F., Letcher, A. J., Heslop, J. P. & Berridge, M. J. Nature 320, 631–634 (1986).
    Article ADS CAS Google Scholar
  18. Kuo, J. F. et al. Proc. natn. Acad. Sci. U.S.A. 77, 7039–7043 (1980).
    Article ADS CAS Google Scholar
  19. Henkart, M., Landis, D. M. D. & Reese, T. S. J. Cell Biol. 70, 338–347 (1976).
    Article CAS Google Scholar
  20. Fifkova, E., Markham, J. A. & Delay, R. J. Brain Res. 166, 163–168 (1983).
    Article Google Scholar
  21. Burgoyne, R. D., Gray, E. G. & Barron, J. J. Anat. 136, 634–635 (1983).
    Google Scholar
  22. Llinas, R. & Sugimori, M. J. Physiol., Lond. 305, 197–213 (1980).
    Article CAS Google Scholar
  23. Kuhar, M. J., Whitehouse, P. J., Unnerstall, J. R. & Loats, H. J. Neurosci. Meth. 6, 59–73 (1982).
    Article Google Scholar

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Authors and Affiliations

  1. Departments of Neuroscience, Pharmacology and Experimental Therapeutics, Psychiatry and Behavioral Sciences, The Johns Hopkins University Medical Institutions, Baltimore, Maryland, 21205, USA
    Paul F. Worley, Jay M. Baraban, Jennifer S. Colvin & Solomon H. Snyder
  2. Department of Neurology, The Johns Hopkins University Medical Institutions, 725 North Wolfe Street, Baltimore, Maryland, 21205, USA
    Paul F. Worley

Authors

  1. Paul F. Worley
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  2. Jay M. Baraban
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  3. Jennifer S. Colvin
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  4. Solomon H. Snyder
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Worley, P., Baraban, J., Colvin, J. et al. Inositol trisphosphate receptor localization in brain: variable stoichiometry with protein kinase C.Nature 325, 159–161 (1987). https://doi.org/10.1038/325159a0

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