Second messenger specificity of the inositol trisphophate receptor: Reappraisal based on novel inositol phosphates

S. DeLisle, T. Radenberg, M. R. Wintermantel, C. Tietz, J. B. Parys, D. Pittet, M. J. Welsh, G. W. Mayr

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

To further understand how the second messenger D-myo-inositol 1,4,5- trisphosphate [Ins(1,4,5)P3] interacts with its intracellular receptor, we injected 47 highly purified inositol phosphate (InsP) positional isomers in Xenopus oocytes and compared their potency in releasing intracellular Ca2+. The potency of the Ca2+-releasing InsPs spanned four orders of magnitude. Seven compounds, including the novel inositol 1,2,4,5-tetrakisphosphate [D/L- Ins(1,2,4,5)P4] and D/L-Ins(1,4,6)P3, had a very high potency. All of these highly active InsPs shared the following structure: two D-trans-equatorial phosphates (eq-P) and one equatorial hydroxyl (eq-OH) attached to ring carbons D-4, D-5, and D-6 (or to the structurally equivalent D-1, D-6, and D- 5 carbons). This permissive structure was not sufficient for Ca2+ release, because it was also found in two inactive compounds, Ins(1,6)P2 and Ins(1,3,6)P3. To be active, InsPs also required the structural equivalent of a D-3 eq-OH and/or a D-1 eq-P. Together, our data reveal how the structure of the InsP molecule affects its ability to release Ca2+.

Original languageEnglish (US)
Pages (from-to)C429-C436
JournalAmerican Journal of Physiology - Cell Physiology
Volume266
Issue number2 35-2
StatePublished - Jan 1 1994

Keywords

  • Xenopus oocyte
  • inositol 1,4,5-trisphosphate

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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    DeLisle, S., Radenberg, T., Wintermantel, M. R., Tietz, C., Parys, J. B., Pittet, D., Welsh, M. J., & Mayr, G. W. (1994). Second messenger specificity of the inositol trisphophate receptor: Reappraisal based on novel inositol phosphates. American Journal of Physiology - Cell Physiology, 266(2 35-2), C429-C436.