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Second messenger specificity of the inositol trisphosphate receptor: reappraisal based on novel inositol phosphates

DeLisle, S.
Radenberg, T.
Wintermantel, M. R.
Tietz, C.
Parys, J. B.
Welsh, M. J.
Mayr, G. W.
Published in American Journal of Physiology. 1994, vol. 266, no. 2 Pt 1, p. C429-436
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+.
Keywords AnimalsCalcium/metabolismCalcium Channels/ metabolismInositol 1,4,5-Trisphosphate ReceptorsInositol Phosphates/ chemistry/ pharmacologyIntracellular Membranes/metabolismOocytes/metabolismReceptors, Cytoplasmic and Nuclear/ metabolismSecond Messenger SystemsStructure-Activity RelationshipXenopus
PMID: 8141257
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Other version: http://ajpcell.physiology.org/cgi/reprint/266/2/C429.pdf
Research group Staphylocoques dorés résistants à la méthicilline et hygiène hospitalière (330)
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DELISLE, S. et al. Second messenger specificity of the inositol trisphosphate receptor: reappraisal based on novel inositol phosphates. In: American Journal of Physiology, 1994, vol. 266, n° 2 Pt 1, p. C429-436. https://archive-ouverte.unige.ch/unige:7160

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Deposited on : 2010-06-21

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