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Title: Inhibition of inositol trisphosphate-induced calcium release by cyclic ADP-ribose in A7r5 smooth-muscle cells and in 16HBE14o- bronchial mucosal cells
Authors: Missiaen, Ludwig
Parys, Jan
De Smedt, Humbert
Sienaert, Ilse
Sipma, Henk
Vanlingen, Sara
Maes, K
Kunzelmann, K
Casteels, Rik #
Issue Date: Mar-1998
Series Title: The Biochemical journal. vol:329 ( Pt 3) pages:489-95
Abstract: Ca2+ release from intracellular stores occurs via two families of intracellular channels, each with their own specific agonist: Ins(1, 4,5)P3 for the Ins(1,4,5)P3 receptor and cyclic ADP-ribose (cADPR) for the ryanodine receptor. We now report that cADPR inhibited Ins(1, 4,5)P3-induced Ca2+ release in permeabilized A7r5 cells with an IC50 of 20 microM, and in permeabilized 16HBE14o- bronchial mucosal cells with an IC50 of 35 microM. This inhibition was accompanied by an increase in specific [3H]Ins(1,4,5)P3 binding. 8-Amino-cADPR, but not 8-bromo-cADPR, antagonized this effect of cADPR. The inhibition was prevented by a whole series of inositol phosphates (10 microM) that did not affect Ins(1,4,5)P3-induced Ca2+ release, and by micromolar concentrations of PPi and various nucleotide di- or triphosphates. We propose that cADPR must interact with a novel regulatory site on the Ins(1,4,5)P3 receptor or on an associated protein. This site is neither the Ins(1,4,5)P3-binding domain, which prefers Ins(1,4,5)P3 and only binds nucleotides and PPi in the millimolar range, nor the stimulatory adenine nucleotide binding site.
ISSN: 0264-6021
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Physiology Section (-)
Laboratory of Molecular and Cellular Signaling
# (joint) last author

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