Inhibitors of Ca2+ channels, calmodulin and protein kinases prevent A23187 and other inductions of metallothionein mRNA in EC3 rat hepatoma cells.

The role of calcium in the induction of MT mRNA has been studied in EC3 rat hepatoma cells, using various inducers (A23187, TPA, norepinephrine, and 2-chloroadenosine) and inhibitors (H7:PK-A and PK-C; W7:calmodulin; verapamil:calcium channel blocker; and TMB-8; cytosolic calcium chelator). The inhibitions of inductions observed in this study were consistent with calcium playing an important role in MT mRNA induction by itself and via crosstalk among the PK-A, PK-C, and calmodulin-dependent protein kinase pathways. Calcium has an important role in the complicated second messenger pathways which result in the positive interaction of transcription factors with the promoters of MT genes.