CALCIUM-MOBILIZING EFFECTORS INHIBIT P-ENOLPYRUVATE CARBOXYKINASE GENE-EXPRESSION IN CULTURED RAT HEPATOCYTES

Incubation of primary cultures of hepatocytes from fed and fasted rats with calcium ionophore strongly decreased glucose production from pyr uvate. Like insulin, calcium ionophore A23187, phenylephrine, vasopres sin, and prostaglandins E2 and F2alpha caused a significant reduction (50-60%) in basal concentrations of mRNA for P-enolpyruvate carboxykin ase (PEPCK), the main regulatory enzyme of gluconeogenesis. Phenylephr ine, prostaglandin E2 and calcium ionophore A23187 were also able to c ounteract the induction of PEPCK gene expression by Bt2cAMP. These eff ects were similar to those exerted by both vanadate and phorbol ester TPA. The decrease in extracellular calcium by the addition of the calc ium-chelating agent EGTA to the incubation medium caused an increase i n PEPCK mRNA levels. This effect was additive to.that of Bt2cAMP and w as counteracted by vanadate.