Stimulation of Phospholipase A(2) by Toxic Main Group Heavy Metals: Partly Dependent on G-proteins?
Organometals induce platelet aggregation and inorganic metal ions such as Cd(2+) or Pb(2+) sensitise human blood platelets to aggregating agents and this action is associated with the liberation of arachidonic acid and eicosanoid formation. The same mechanism is observed using human leukaemia cells (HL-60) when treated with MeHgCl or Et(3)PbCl. The fatty acid liberation within human platelets and HL-60 cells could only be inhibited with phospholipase A(2) inhibitors of different specificity.Preincubation of the cells with pertussis toxin reduces the activation induced by Et(3)PbCl to a great extent. The non-catalytic B subunit, that only mediates the binding of the toxin to the cell membranes, has no effect at all. When summarised, these results suggest that one possible mechanism for the stimulation of phospholipase A(2) by Et(3)PbCl functions via a G-protein dependent pathway.
Krug
H F
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Kernforschungszentrum Karlsruhe Institute of Toxicology P.O. Box 3640 Karlsruhe D-76021 Germany.