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 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Cell Physiology
Volume266
Issue number2 35-2
StatePublished - Jan 1 1994

Fingerprint

Inositol Phosphates
Second Messenger Systems
Inositol
Hydroxyl Radical
Carbon
Inositol 1,4,5-Trisphosphate
Xenopus
Isomers
Oocytes
Phosphates
Molecules
inositol-1,2,4,5-tetrakisphosphate

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

DeLisle, S., Radenberg, T., Wintermantel, M. R., Tietz, C., Parys, J. B., Pittet, D., ... 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).

Second messenger specificity of the inositol trisphophate receptor : Reappraisal based on novel inositol phosphates. / DeLisle, S.; Radenberg, T.; Wintermantel, M. R.; Tietz, C.; Parys, J. B.; Pittet, D.; Welsh, M. J.; Mayr, G. W.

In: American Journal of Physiology - Cell Physiology, Vol. 266, No. 2 35-2, 01.01.1994.

Research output: Contribution to journalArticle

DeLisle, S, Radenberg, T, Wintermantel, MR, Tietz, C, Parys, JB, Pittet, D, Welsh, MJ & Mayr, GW 1994, 'Second messenger specificity of the inositol trisphophate receptor: Reappraisal based on novel inositol phosphates', American Journal of Physiology - Cell Physiology, vol. 266, no. 2 35-2.
DeLisle, S. ; Radenberg, T. ; Wintermantel, M. R. ; Tietz, C. ; Parys, J. B. ; Pittet, D. ; Welsh, M. J. ; Mayr, G. W. / Second messenger specificity of the inositol trisphophate receptor : Reappraisal based on novel inositol phosphates. In: American Journal of Physiology - Cell Physiology. 1994 ; Vol. 266, No. 2 35-2.
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