Unknown

Dataset Information

0

Inhibition of inositol trisphosphate-induced calcium release by cyclic ADP-ribose in A7r5 smooth-muscle cells and in 16HBE14o- bronchial mucosal cells.


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.

SUBMITTER: Missiaen L 

PROVIDER: S-EPMC1219068 | BioStudies | 1998-01-01

SECONDARY ACCESSION(S): 10.1042/bj3290489

REPOSITORIES: biostudies

Similar Datasets

1991-01-01 | S-EPMC1151159 | BioStudies
1997-01-01 | S-EPMC1218609 | BioStudies
1994-01-01 | S-EPMC1137122 | BioStudies
1990-01-01 | S-EPMC1149731 | BioStudies
1990-01-01 | S-EPMC1133688 | BioStudies
1992-01-01 | S-EPMC1132037 | BioStudies
1990-01-01 | S-EPMC1149781 | BioStudies
1989-01-01 | S-EPMC1138567 | BioStudies
1986-01-01 | S-EPMC1153089 | BioStudies
1997-01-01 | S-EPMC1218891 | BioStudies