Specific Receptors for Inositol 1,4,5-Trisphosphate in Endocrine Target Tissues

  • Gaetan Guillemette
  • Tamas Balla
  • Albert J. Baukal
  • Kevin J. Catt
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


The hydrolysis of inositol lipids by phospholipase C is believed to be the primary mechanism by which many hormones elicit calcium-mediated metabolic and secretory responses in their respective target tissues. The initiating event in this signaling system is the phosphodiesteratic cleavage of phosphatidylinositol-4,5-bisphosphate to generate the inositol-1,4,5-trisphosphate (IP3), which can mobilize intracellular Ca2+(Berridge and Irvine, 1984), and 1,2 diacylglycerol, which stimulates protein kinase C (Nishizuka, 1984). IP3has been shown to release Ca2+ from nonmitochondrial stores in a wide variety of cells (Strebet al., 1983; Josephet al., 1984; for review see Abdel-Latif, 1986). The mechanism of IP3-induced Ca2+ release is not yet known but it has been postulated that IP3interacts with a specific receptor on the endoplasmic reticulum. The purpose of this chapter is to describe the properties of specific binding sites for IP3in subcellular preparations of the adrenal cortex, the anterior pituitary gland, and the liver. The physiological relevance of these putative receptors is assessed by the study of Ca2+ -releasing activity of IP3in the same tissue preparations.


Phytic Acid Adrenal Cortex Anterior Pituitary Gland Liver Plasma Membrane Plasma Membrane Fraction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abdel-Latif, A. A. 1986, Calcium-mobilizing receptors, polyphosphoinositides, and the generation of second messengers, Pharmacol. Revs. 38:227–272.Google Scholar
  2. Balla, T., Guillemette, G., Baukal, A. J., and Catt, K. J., 1988, Multiple pathways of inositol polyphosphate metabolism in angiotensin-stimulated adrenal glomerulosa cells, J. Biol. Chem. 263: 4083–4091.PubMedGoogle Scholar
  3. Baukal, A. J., Guillemette, G., Rubin, R., Spat, A., and Catt, K. J., 1985, Binding sites for inositol trisphosphate in the bovine adrenal cortex, Biochem. Biophys. Res. Commun. 133:532–538.PubMedCrossRefGoogle Scholar
  4. Berridge, M. J., and Irvine, R. F., 1984, Inositol trisphosphate, a novel second messenger in cellular signal transduction, Nature 312:315–321.PubMedCrossRefGoogle Scholar
  5. Chueh, S.-H., and Gill, D. L., 1986, Inositol 1,4,5-trisphosphate and guanine nucleotides activate calcium release from endoplasmic reticulum via distinct mechanisms, J. Biol. Chem. 261:13883–13886.PubMedGoogle Scholar
  6. Dawson, A. P., and Irvine, R. F., 1984, Inositol trisphosphate-promoted Ca2+ release from microsomal fractions of rat liver, Biochem. Biophys. Res. Commun. 120:858–864.PubMedCrossRefGoogle Scholar
  7. Dawson, A. P., 1985, GTP enhances inositol trisphosphate-stimulated Ca2+ release from rat liver microsomes, FEBS Lett. 185:147–150.PubMedCrossRefGoogle Scholar
  8. Guillemette, G., Balla, T., Baukal, A. J., Spat, A., and Catt, K. J., 1987a, Intracellular receptors for inositol 1,4,5-trisphosphate in angiotension II target tissues, J. Biol. Chem. 262:1010–1015.PubMedGoogle Scholar
  9. Guillemette, G., Balla, T., Baukal, A. J., and Catt, K. J., 1987b, Inositol-1,4,5-trisphosphate binds to a specific receptor and releases microsomal calcium in the anterior pituitary gland, Proc. Natl. Acad. Sci. USA 84:8195–8199.PubMedCrossRefGoogle Scholar
  10. Guillemette, G., Balla, T., Baukal, A. J., and Catt, K. J., 1988, Characterization of inositol 1,4,5 trisphosphate receptors and calcium mobilization in a hepatic plasma membrane fraction, J. Biol. Chem. 263:4541–4548.PubMedGoogle Scholar
  11. Guillemette, G., Baukal, A. J., Balla, T., and Catt, K. J., 1987c, Angiotension-induced formation and metabolism of inositol polyphosphates in bovine adrenal glomerulosa cells, Biochem. Biophys. Res. Commun. 142:15–22.PubMedCrossRefGoogle Scholar
  12. Hamachi, T., Hirata, M., Kimura, Y., Ikebe, T., Ishimatsu, T., Yamaguchi, K., and Koga, T., 1987, Effect of guanosine triphosphate on the release and uptake of Ca2+ in the saponin-permeabilized macrophages and the skeletal-muscle sarcoplasmic reticulum, Biochem. J. 242:253–260.PubMedGoogle Scholar
  13. Hansen, C. A., Mag, S., and Williamson, J. R., 1986, Formation and metabolism of inositol 1,3,4,5-tetrakisphosphate in liver, J. Biol. Chem. 261:8100–8103.PubMedGoogle Scholar
  14. Hawkins, P. T., Stephens, L., and Downes, C. P., 1986, Rapid formation of inositol 1,3,4,5-tetrak-isphosphate and inositol 1,3,4-trisphosphate in rat parotid glands may both result indirectly from receptor-stimulated release of inositol 1,4,5-trisphosphate from phospatidylinositol 4,5-bisphos-phate, Biochem J. 238:507–516.PubMedGoogle Scholar
  15. Hirata, M., Sasaguri, T., Hamashi, T., Hashimoto, T., Kukita, M., and Koga, T., 1985, Irreversible inhibition of Ca2+ release in saponin-treated macrophages by the photoaffinity derivative of inositol-1,4,5-trisphosphate, Nature 317:723–725.PubMedCrossRefGoogle Scholar
  16. Irvine, R. F., Letcher, A. J., Heslop, J. P., and Berridge, M. J., 1986, The inositol tris/tetrakisphosphate pathway-demonstration of ins (1,4,5)P3 3-kinase activity in animal tissues, Nature 320:631–634.PubMedCrossRefGoogle Scholar
  17. Jean, T., and Klee, C. B., 1986, Calcium modulation of inositol 1,4,5-trisphosphate-induced calcium release from neuroblastoma X glioma hybrid (NG108–15) microsomes, J. Biol. Chem. 261: 16414–16420.PubMedGoogle Scholar
  18. Joseph, S. K., Thomas, A. P., Williams, R. J., Irvine, R. F., and Williamson, J. R., 1984, Myo-inositol 1,4,5-trisphosphate: A second messenger for the hormonal mobilization of intracellular Ca2+ in liver, J. Biol. Chem. 259:3077–3081.PubMedGoogle Scholar
  19. Joseph, S. K., and Williamson, J. R., 1986, Characteristics of inositol trisphosphate-mediated release from permeabilized hepatocytes, J. Biol. Chem. 261:14658–14664.PubMedGoogle Scholar
  20. Kuno, M., and Gardner, P., 1987, Ion channels activated by inositol 1,4,5-trisphosphate in plasma membrane of human T-lymphocytes, Nature 326:301–304.PubMedCrossRefGoogle Scholar
  21. Neville, D. M., Jr., 1968, Isolation of an organ specific protein antigen from cell-surface membrane of rat liver, Biochem. Biophys. Acta 154:540–552.PubMedGoogle Scholar
  22. Nishizuka, Y., 1984, The role of protein kinase C in cell surface signal transduction and tumor promotion, Nature 308:693–698.PubMedCrossRefGoogle Scholar
  23. Putney, J. W., Jr., 1986, A model for receptor-regulated calcium entry, Cell Calcium 7:1–12.PubMedCrossRefGoogle Scholar
  24. Seyfred, M. A., Farrell, L. E., and Wells, W. W., 1984, Characterization of D-myo-inositol 1,4,5 trisphosphate phosphatose in rat liver plasma membranes, J. Biol. Chem. 259:13204–13208.PubMedGoogle Scholar
  25. Spat, A., Fabiato, A., and Rubin, R. P., 1986a, Binding of inositol trisphosphate by a liver microsomal fraction, Biochem. J. 233:929–932.PubMedGoogle Scholar
  26. Spat, A., Bradford, P. G., McKinney, V. S., Rubin, R. P., and Putney, J. W. Jr., 1986b, A saturable receptor for 32Pinositol-1,4,5-trisphosphate in hepatocytes and neutrophyls, Nature 319:514–516.PubMedCrossRefGoogle Scholar
  27. Storey, D. J., Shears, S. B., Kirk, C. J., and Michell, R. H.,1984, Stepwise enzymatic dephosphor-ylation of inositol 1,4,5-trisphosphate to inositol in liver, Nature 312:374–376.PubMedCrossRefGoogle Scholar
  28. Streb, H., Irvine, R. F., Berridge, M. J., and Schulz, I., 1983, Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol 1,4,5-trisphosphate, Nature 306:67–69.PubMedCrossRefGoogle Scholar
  29. Worley, P. F., Baraban, J. M., Colvin, J. S., and Snyder, S. H.,1987, Inositol trisphosphate receptor localization in brain: variable stoichiometry with protein kinase C., Nature 325:159–161.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Gaetan Guillemette
    • 1
  • Tamas Balla
    • 1
  • Albert J. Baukal
    • 1
  • Kevin J. Catt
    • 1
  1. 1.Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaUSA

Personalised recommendations