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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| Authors: | P C Wood R J H Wojcikiewicz J Burgess† C M Castleden S R Nahorski |
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| Institution: | Department of Medicine for the Elderly, University of Leicester, Leicester, England;Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, England;Department of Chemistry, University of Leicester, Leicester, England |
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| Abstract: | 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 μ M ). Aβ3+ also inhibited lnsP3 production (lC60 of ～15 μ M ). Dimethyl hydroxypyridin-4-one, a potent Al3+ chelator (K5= 31), at 100 μ M 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. |
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| Keywords: | Aluminium Calcium Inositol trisphosphate Muscarinic receptors SH-SY5Y cells |
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