title: Aluminium perturbs oscillatory phosphoinositide-mediated calcium signalling in hormone-stimulated hepatocytes.
abstract: Aluminium is known to be toxic to cells from bone, brain and bone marrow but the molecular target(s) affected by Al3+ are not known. We show here that Al3+ disrupts the oscillatory free Ca2+ responses of hepatocytes exposed to the Ca2(+)-mobilizing agonist phenylephrine. Al3+ initially increases the frequency of the oscillations and later induces broad Ca2+ spikes lasting several minutes. These broad spikes persist after removal of both agonist and Al3+ from the medium. In the absence of agonist, Al3+ has no effect on free Ca2+. The data suggest that some component(s) of the receptor-phosphoinositide-Ca2+ signalling pathway might be the site at which Al3+ exerts toxic effects.
authors.affiliation: Department of Human Anatomy and Cell Biology, University of Liverpool, U.K.
authors.forename: C
authors.initials: C
authors.lastname: Schöfl
authors.forename: A
authors.initials: A
authors.lastname: Sanchez-Bueno
authors.forename: C J
authors.initials: CJ
authors.lastname: Dixon
authors.forename: N M
authors.initials: NM
authors.lastname: Woods
authors.forename: J A
authors.initials: JA
authors.lastname: Lee
authors.forename: K S
authors.initials: KS
authors.lastname: Cuthbertson
authors.forename: P H
authors.initials: PH
authors.lastname: Cobbold
authors.forename: J D
authors.initials: JD
authors.lastname: Birchall
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D003676:Deferoxamine / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010507:Periodicity; D010656:Phenylephrine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002951:Citrates; D010716:Phosphatidylinositols; D010656:Phenylephrine; D019343:Citric Acid; D003676:Deferoxamine; D002118:Calcium