Premium
Aluminium Inhibits Muscarinic Agonist‐Induced Inositol 1,4,5‐Trisphosphate Production and Calcium Mobilization in Permeabilized SH‐SY5Y Human Neuroblastoma Cells
Author(s) -
Wood P. C.,
Wojcikiewicz R. J. H.,
Burgess J.,
Castleden C. M.,
Nahorski S. R.
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.62062219.x
Subject(s) - inositol , sh sy5y , carbachol , phosphatidylinositol , phospholipase c , muscarinic acetylcholine receptor , chemistry , phosphatidylinositol 4,5 bisphosphate , inositol trisphosphate receptor , agonist , inositol trisphosphate , endocrinology , calcium , medicine , biophysics , receptor , signal transduction , biochemistry , biology , neuroblastoma , cell culture , organic chemistry , genetics
The effects of aluminium (as Al 3+ ) on carbachol‐induced inositol 1,4,5‐trisphosphate (lnsP 3 ) production arid Ca 2+ mobilisation were assessed in electropermeabilised human SH‐SY5Y neuroblastoma cells. Al 3+ had no effect on lnsP 3 ‐induced Ca 2+ release but appreciably reduced carbachol‐induced Ca 2+ release (lC 50 of ∼90 μ M ). Aβ 3+ also inhibited lnsP 3 production (lC 60 of ∼15 μ M ). Dimethyl hydroxypyridin‐4‐one, a potent Al 3+ chelator (K 5 = 31), at 100 μ M was able to abort and reverse the effects of Al 3+ on both Ca 2+ release and lnsP 3 production. These data suggest that, in permeabilised cells, the effect of Al 3+ on the phosphoinositide‐mediated signalling pathway is at the level of phosphatidylinositol 4,5‐bisphosphate hydrolysis. This may reflect interference with receptor‐G protein‐phospholipase C coupling or an interaction with phosphatidylinositol 4,5‐bisphosphate.