Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1996 Mar 15;314(Pt 3):811–816. doi: 10.1042/bj3140811

Synergistic effects of inositol 1,3,4,5-tetrakisphosphate on inositol 2,4,5-triphosphate-stimulated Ca2+ release do not involve direct interaction of inositol 1,3,4,5-tetrakisphosphate with inositol triphosphate-binding sites.

J W Loomis-Husselbee 1, P J Cullen 1, U E Dreikausen 1, R F Irvine 1, A P Dawson 1
PMCID: PMC1217129  PMID: 8615774

Abstract

We have previously found that for permeabilized L1210 cells, low micromolar concentrations of Ins(1,3,4,5)P4 added prior to Ins(2,4,5)P3 enhance the effects of suboptimal concentrations of Ins(2,4,5)P3 in causing Ca2+ release from InsP3-sensitive Ca2+ stores [Cullen, Irvine and Dawson (1990) Biochem J. 271, 549-553]. If this was due either to some conversion of added Ins(1,3,4,5)P4 into Ins(1,4,5)P3 by the 3-phosphatase, or to Ins(1,3,4,5)P4 acting as a weak (or partial) agonist on the InsP3 receptor it would be expected that,in the presence of thimerosal to sensitize the InsP3 receptor, the dose-response curve to Ins(1,3,4,5)P4 would be left-shifted by the same extent as that of Ins(1,4,5)P3. This was found not to be the case; the dose-response curve to Ins(1,3,4,5)P4 was not shifted at all by thimerosal. Furthermore, L-Ins(1,3,4,5)P4, which can displace radiolabelled D-Ins(1,3,4,5)P4 but not D-Ins(1,4,5)P3 from their respective high-affinity binding sites, mimicked the effects of D-Ins(1,3,4,5)P4 in enhancing the slow phase of Ins(2,4,5)P3-stimulated Ca2+ release. Ins(1,3,4,5)P4 caused an increase in magnitude of the slow phase of InsP3-stimulated Ca2+ release leaving the magnitude of the fast phase unaltered, in contrast to increasing Ins(2,4,5)P3 concentrations which increased the size of both phases. In addition, Ins(1,3,4,5)P4 decreased the rate constant for the slow phase of Ca2+ release. These findings point strongly to the conclusion that InsP4 is not working directly via the InsP3 receptor but indirectly via an InsP4 receptor.

Full Text

The Full Text of this article is available as a PDF (441.9 KB).

Selected References

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

  1. Changya L., Gallacher D. V., Irvine R. F., Potter B. V., Petersen O. H. Inositol 1,3,4,5-tetrakisphosphate is essential for sustained activation of the Ca2+-dependent K+ current in single internally perfused mouse lacrimal acinar cells. J Membr Biol. 1989 Jul;109(1):85–93. doi: 10.1007/BF01870793. [DOI] [PubMed] [Google Scholar]
  2. Cullen P. J., Dawson A. P., Irvine R. F. Purification and characterization of an Ins(1,3,4,5)P4 binding protein from pig platelets: possible identification of a novel non-neuronal Ins(1,3,4,5)P4 receptor. Biochem J. 1995 Jan 1;305(Pt 1):139–143. doi: 10.1042/bj3050139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cullen P. J., Hsuan J. J., Truong O., Letcher A. J., Jackson T. R., Dawson A. P., Irvine R. F. Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of the GAP1 family. Nature. 1995 Aug 10;376(6540):527–530. doi: 10.1038/376527a0. [DOI] [PubMed] [Google Scholar]
  4. Cullen P. J., Irvine R. F., Dawson A. P. Synergistic control of Ca2+ mobilization in permeabilized mouse L1210 lymphoma cells by inositol 2,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. Biochem J. 1990 Oct 15;271(2):549–553. doi: 10.1042/bj2710549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cullen P. J., Irvine R. F., Drøbak B. K., Dawson A. P. Inositol 1,3,4,5-tetrakisphosphate causes release of Ca2+ from permeabilized mouse lymphoma L1210 cells by its conversion into inositol 1,4,5-trisphosphate. Biochem J. 1989 May 1;259(3):931–933. doi: 10.1042/bj2590931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ely J. A., Hunyady L., Baukal A. J., Catt K. J. Inositol 1,3,4,5-tetrakisphosphate stimulates calcium release from bovine adrenal microsomes by a mechanism independent of the inositol 1,4,5-trisphosphate receptor. Biochem J. 1990 Jun 1;268(2):333–338. doi: 10.1042/bj2680333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gawler D. J., Potter B. V., Gigg R., Nahorski S. R. Interactions between inositol tris- and tetrakis-phosphates. Effects on intracellular Ca2+ mobilization in SH-SY5Y cells. Biochem J. 1991 May 15;276(Pt 1):163–167. doi: 10.1042/bj2760163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gawler D. J., Potter B. V., Nahorski S. R. Inositol 1,3,4,5-tetrakisphosphate-induced release of intracellular Ca2+ in SH-SY5Y neuroblastoma cells. Biochem J. 1990 Dec 1;272(2):519–524. doi: 10.1042/bj2720519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gyulai L., Roth Z., Leigh J. S., Jr, Chance B. Bioenergetic studies of mitochondrial oxidative phosphorylation using 31phosphorus NMR. J Biol Chem. 1985 Apr 10;260(7):3947–3954. [PubMed] [Google Scholar]
  10. Hajnóczky G., Thomas A. P. The inositol trisphosphate calcium channel is inactivated by inositol trisphosphate. Nature. 1994 Aug 11;370(6489):474–477. doi: 10.1038/370474a0. [DOI] [PubMed] [Google Scholar]
  11. Hashii M., Nozawa Y., Higashida H. Bradykinin-induced cytosolic Ca2+ oscillations and inositol tetrakisphosphate-induced Ca2+ influx in voltage-clamped ras-transformed NIH/3T3 fibroblasts. J Biol Chem. 1993 Sep 15;268(26):19403–19410. [PubMed] [Google Scholar]
  12. Hirota J., Michikawa T., Miyawaki A., Furuichi T., Okura I., Mikoshiba K. Kinetics of calcium release by immunoaffinity-purified inositol 1,4,5-trisphosphate receptor in reconstituted lipid vesicles. J Biol Chem. 1995 Aug 11;270(32):19046–19051. doi: 10.1074/jbc.270.32.19046. [DOI] [PubMed] [Google Scholar]
  13. Irvine R. F., Cullen P. J. Will the real IP4 receptor please stand up? Curr Biol. 1993 Aug 1;3(8):540–543. doi: 10.1016/0960-9822(93)90052-p. [DOI] [PubMed] [Google Scholar]
  14. Irvine R. F. Is inositol tetrakisphosphate the second messenger that controls Ca2+ entry into cells? Adv Second Messenger Phosphoprotein Res. 1992;26:161–185. [PubMed] [Google Scholar]
  15. Irvine R. F., Moor R. M. Micro-injection of inositol 1,3,4,5-tetrakisphosphate activates sea urchin eggs by a mechanism dependent on external Ca2+. Biochem J. 1986 Dec 15;240(3):917–920. doi: 10.1042/bj2400917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Joseph S. K., Hansen C. A., Williamson J. R. Inositol tetrakisphosphate mobilizes calcium from cerebellum microsomes. Mol Pharmacol. 1989 Sep;36(3):391–397. [PubMed] [Google Scholar]
  17. Kaplin A. I., Ferris C. D., Voglmaier S. M., Snyder S. H. Purified reconstituted inositol 1,4,5-trisphosphate receptors. Thiol reagents act directly on receptor protein. J Biol Chem. 1994 Nov 18;269(46):28972–28978. [PubMed] [Google Scholar]
  18. Loomis-Husselbee J. W., Cullen P. J., Irvine R. F., Dawson A. P. Electroporation can cause artefacts due to solubilization of cations from the electrode plates. Aluminum ions enhance conversion of inositol 1,3,4,5-tetrakisphosphate into inositol 1,4,5-trisphosphate in electroporated L1210 cells. Biochem J. 1991 Aug 1;277(Pt 3):883–885. doi: 10.1042/bj2770883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Loomis-Husselbee J. W., Dawson A. P. A steady-state mechanism can account for the properties of inositol 2,4,5-trisphosphate-stimulated Ca2+ release from permeabilized L1210 cells. Biochem J. 1993 Feb 1;289(Pt 3):861–866. doi: 10.1042/bj2890861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lückhoff A., Clapham D. E. Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca(2+)-permeable channel. Nature. 1992 Jan 23;355(6358):356–358. doi: 10.1038/355356a0. [DOI] [PubMed] [Google Scholar]
  21. Meyer T., Holowka D., Stryer L. Highly cooperative opening of calcium channels by inositol 1,4,5-trisphosphate. Science. 1988 Apr 29;240(4852):653–656. doi: 10.1126/science.2452482. [DOI] [PubMed] [Google Scholar]
  22. Meyer T., Stryer L. Transient calcium release induced by successive increments of inositol 1,4,5-trisphosphate. Proc Natl Acad Sci U S A. 1990 May;87(10):3841–3845. doi: 10.1073/pnas.87.10.3841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Missiaen L., Taylor C. W., Berridge M. J. Spontaneous calcium release from inositol trisphosphate-sensitive calcium stores. Nature. 1991 Jul 18;352(6332):241–244. doi: 10.1038/352241a0. [DOI] [PubMed] [Google Scholar]
  24. Morris A. P., Gallacher D. V., Irvine R. F., Petersen O. H. Synergism of inositol trisphosphate and tetrakisphosphate in activating Ca2+-dependent K+ channels. Nature. 1987 Dec 17;330(6149):653–655. doi: 10.1038/330653a0. [DOI] [PubMed] [Google Scholar]
  25. Parker I., Ivorra I. Inositol tetrakisphosphate liberates stored Ca2+ in Xenopus oocytes and facilitates responses to inositol trisphosphate. J Physiol. 1991 Feb;433:207–227. doi: 10.1113/jphysiol.1991.sp018422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Putney J. W., Jr, Bird G. S. The inositol phosphate-calcium signaling system in nonexcitable cells. Endocr Rev. 1993 Oct;14(5):610–631. doi: 10.1210/edrv-14-5-610. [DOI] [PubMed] [Google Scholar]
  27. Sayers L. G., Brown G. R., Michell R. H., Michelangeli F. The effects of thimerosal on calcium uptake and inositol 1,4,5-trisphosphate-induced calcium release in cerebellar microsomes. Biochem J. 1993 Feb 1;289(Pt 3):883–887. doi: 10.1042/bj2890883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smith P. M. Ins(1,3,4,5)P4 promotes sustained activation of the Ca(2+(-dependent Cl- current in isolated mouse lacrimal cells. Biochem J. 1992 Apr 1;283(Pt 1):27–30. doi: 10.1042/bj2830027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Spät A., Lukács G. L., Eberhardt I., Kiesel L., Runnebaum B. Binding of inositol phosphates and induction of Ca2+ release from pituitary microsomal fractions. Biochem J. 1987 Jun 1;244(2):493–496. doi: 10.1042/bj2440493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Swillens S., Combettes L., Champeil P. Transient inositol 1,4,5-trisphosphate-induced Ca2+ release: a model based on regulatory Ca(2+)-binding sites along the permeation pathway. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10074–10078. doi: 10.1073/pnas.91.21.10074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wilcox R. A., Challiss R. A., Baudin G., Vasella A., Potter B. V., Nahorski S. R. Stereoselectivity of Ins(1,3,4,5)P4 recognition sites: implications for the mechanism of the Ins(1,3,4,5)P4-induced Ca2+ mobilization. Biochem J. 1993 Aug 15;294(Pt 1):191–194. doi: 10.1042/bj2940191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wilcox R. A., Challiss R. A., Liu C., Potter B. V., Nahorski S. R. Inositol-1,3,4,5-tetrakisphosphate induces calcium mobilization via the inositol-1,4,5-trisphosphate receptor in SH-SY5Y neuroblastoma cells. Mol Pharmacol. 1993 Oct;44(4):810–817. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES