ALUMINUM INHIBITS MUSCARINIC AGONIST-INDUCED INOSITOL 1,4,5-TRISPHOSPHATE PRODUCTION AND CALCIUM MOBILIZATION IN PERMEABILIZED SH-SY5Y HUMAN NEUROBLASTOMA-CELLS

The effects of aluminium (as Al3+) on carbachol-induced inositol 1,4,5 -trisphosphate (InsP(3)) production and Ca2+ mobilisation were assesse d in electropermeabilised human SH-SY5Y neuroblastoma cells. Al3+ had no effect on InsP(3)-induced Ca2+ release but appreciably reduced carb achol-induced Ca2+ release (IC50 of similar to 90 mu M). Al3+ also inh ibited InsP(3) production (IC50 of similar to 15 mu M). Dimethyl hydro xypyridin-4-one, a potent Al3+ chelator (K-S = 31), at 100 mu M was ab le to abort and reverse the effects of Al3+ on both Ca2+ release and I nsP(3) production. These data suggest that, in permeabilised cells, th e effect of Al3+ on the phosphoinositide-mediated signalling pathway i s at the level of phosphatidylinositol 4,5-bisphosphate hydrolysis. Th is may reflect interference with receptor-G protein-phospholipase C co upling or an interaction with phosphatidylinositol 4,5-bisphosphate.