Aluminium Inhibits Muscarinic Agonist-Induced Inositol 1,4,5-Trisphosphate Production and Calcium Mobilization in Permeabilized SH-SY5Y Human Neuroblastoma Cells
Article first published online: 28 JUN 2008
Journal of Neurochemistry
Volume 62, Issue 6, pages 2219–2223, June 1994
How to Cite
Wood, P. C., Wojcikiewicz, R. J. H., Burgess, J., Castleden, C. M. and Nahorski, S. R. (1994), Aluminium Inhibits Muscarinic Agonist-Induced Inositol 1,4,5-Trisphosphate Production and Calcium Mobilization in Permeabilized SH-SY5Y Human Neuroblastoma Cells. Journal of Neurochemistry, 62: 2219–2223. doi: 10.1046/j.1471-4159.1994.62062219.x
- Issue published online: 28 JUN 2008
- Article first published online: 28 JUN 2008
- Received July 9, 1993; revised manuscript received October 12, 1993; accepted October 12, 1993.
- Inositol trisphosphate;
- Muscarinic receptors;
- SH-SY5Y cells
Abstract: The effects of aluminium (as Al3+) on carbachol-induced inositol 1,4,5-trisphosphate (lnsP3) production arid Ca2+ mobilisation were assessed in electropermeabilised human SH-SY5Y neuroblastoma cells. Al3+ had no effect on lnsP3-induced Ca2+ release but appreciably reduced carbachol-induced Ca2+ release (lC50 of ∼90 μM). Aβ3+ also inhibited lnsP3 production (lC60 of ∼15 μM). Dimethyl hydroxypyridin-4-one, a potent Al3+ chelator (K5= 31), at 100 μM was able to abort and reverse the effects of Al3+ on both Ca2+ release and lnsP3 production. These data suggest that, in permeabilised cells, the effect of Al3+ 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.