Induction of metallothionein in rat liver by cadmium chloride: probable mechanism of action.

The mechanism of action of cadmium in the inductive pathway of metallothionein (MT) synthesis was studied in the rat. Cadmium significantly elevated the MT level by 872% which was antagonised by coadministration of either verapamil (343.5%) or ionophore (570%). The Ca-dependent biomolecules such as cyclic AMP or calmodulin remained depressed in all treatment regimens except calmodulin in the ionophore treated rat. Total Ca2+ showed no increase in its profile except in the ionophore treatments either alone or with CdCl2. The Na+ profile is, however, significantly elevated in all cases except the ionophore treated rat. The present study clearly indicates that (a) Ca2+ has no first messenger role in the schematic events leading to MT synthesis and (b) Na+ may be regarded as a possible candidate in the molecular events of Cd-induced MT synthesis.