The effect of signal transduction-related factors was investigated to clarify the expression mechanism for mRNA of the hepatic Ca(2+)-binding protein regucalcin in the liver of rats. The change of regucalcin mRNA levels was analyzed by Northern blotting using liver regucalcin cDNA (0.6 kb). A single intraperitoneal administration of calcium chloride (15 mg Ca2+: 0.374 mmol/100 g body weight) to rats induced a remarkable increase of regucalcin mRNA in liver; the level was about 170% of controls at 30 min after administration. This increase was completely inhibited by simultaneous administration of trifluoperazine (5.0 mg/100 g), an antagonist of calmodulin. On the other hand, a single intraperitoneal administration of phorbol ester or dibutyryl cAMP (10-1,000 micrograms/100 g) did not cause a significant alteration of hepatic regucalcin mRNA levels. Also, administration of zinc, copper and cadmium (0.374 mmol of metal ion/100 g) did not have an appreciable effect on hepatic regucalcin mRNA levels. These findings demonstrate that the expression of hepatic regucalcin mRNA is mediated through Ca2+/calmodulin.