Aluminium perturbs oscillatory phosphoinositide-mediated calcium signalling in hormone-stimulated hepatocytes.
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.
Schöfl
C
C
Department of Human Anatomy and Cell Biology, University of Liverpool, U.K.
Sanchez-Bueno
A
A
Dixon
C J
CJ
Woods
N M
NM
Lee
J A
JA
Cuthbertson
K S
KS
Cobbold
P H
PH
Birchall
J D
JD
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*
D002951:Citrates; D010716:Phosphatidylinositols; D010656:Phenylephrine; D019343:Citric Acid; D003676:Deferoxamine; D002118:Calcium