Journal article
Second messenger specificity of the inositol trisphosphate receptor: reappraisal based on novel inositol phosphates
American Journal of Physiology: Cell Physiology, Vol.266(2), pp.C429-C436
02/01/1994
DOI: 10.1152/ajpcell.1994.266.2.C429
PMID: 8141257
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 Ca(2+)-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+.
Details
- Title: Subtitle
- Second messenger specificity of the inositol trisphosphate receptor: reappraisal based on novel inositol phosphates
- Creators
- Sylvain Delisle - Howard Hughes Medical Institute, Department of Internal Medicine,University of Iowa College of Medicine, Iowa City 52242Thomas Radenberg - Howard Hughes Medical Institute, Department of Internal Medicine,University of Iowa College of Medicine, Iowa City 52242Mary R Wintermantel - Howard Hughes Medical Institute, Department of Internal Medicine,University of Iowa College of Medicine, Iowa City 52242Cornelia Tietz - Howard Hughes Medical Institute, Department of Internal Medicine,University of Iowa College of Medicine, Iowa City 52242Jan B Parys - Howard Hughes Medical Institute, Department of Internal Medicine,University of Iowa College of Medicine, Iowa City 52242Didier Pittet - Howard Hughes Medical Institute, Department of Internal Medicine,University of Iowa College of Medicine, Iowa City 52242Michael J Welsh - Howard Hughes Medical Institute, Department of Internal Medicine,University of Iowa College of Medicine, Iowa City 52242Georg W Mayr - Howard Hughes Medical Institute, Department of Internal Medicine,University of Iowa College of Medicine, Iowa City 52242
- Resource Type
- Journal article
- Publication Details
- American Journal of Physiology: Cell Physiology, Vol.266(2), pp.C429-C436
- DOI
- 10.1152/ajpcell.1994.266.2.C429
- PMID
- 8141257
- NLM abbreviation
- Am J Physiol Cell Physiol
- ISSN
- 0363-6143
- eISSN
- 1522-1563
- Language
- English
- Date published
- 02/01/1994
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020711602771
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