Aluminium 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 (InsP3) production and Ca2+ mobilisation were assessed in electropermeabilised human SH-SY5Y neuroblastoma cells. Al3+ had no effect on InsP3-induced Ca2+ release but appreciably reduced carbachol-induced Ca2+ release (IC50 of approximately 90 microM). Al3+ also inhibited InsP3 production (IC50 of approximately 15 microM). Dimethyl hydroxypyridin-4-one, a potent Al3+ chelator (Ks = 31), at 100 microM was able to abort and reverse the effects of Al3+ on both Ca2+ release and InsP3 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.
Wood
P C
PC
Department of Medicine for the Elderly, University of Leicester, England.
Wojcikiewicz
R J
RJ
Burgess
J
J
Castleden
C M
CM
Nahorski
S R
SR
D000535:Aluminum / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010277:Parasympathomimetics / Q000494:pharmacology*; D010539:Permeability; D014407:Tumor Cells, Cultured
D010277:Parasympathomimetics; D015544:Inositol 1,4,5-Trisphosphate; D000535:Aluminum; D002118:Calcium