Aluminium Inhibits Muscarinic Agonist‐Induced Inositol 1,4,5‐Trisphosphate Production and Calcium Mobilization in Permeabilized SH‐SY5Y Human Neuroblastoma Cells

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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.