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 pyruvate. Like insulin, calcium ionophore A23187, phenylephrine, vasopressin, and prostaglandins E2 and F2 alpha caused a significant reduction (50-60%) in basal concentrations of mRNA for P-enolpyruvate carboxykinase (PEPCK), the main regulatory enzyme of gluconeogenesis. Phenylephrine, prostaglandin E2 and calcium ionophore A23187 were also able to counteract the induction of PEPCK gene expression by Bt2cAMP. These effects were similar to those exerted by both vanadate and phorbol ester TPA. The decrease in extracellular calcium by the addition of the calcium-chelating agent EGTA to the incubation medium caused an increase in PEPCK mRNA levels. This effect was additive to that of Bt2cAMP and was counteracted by vanadate.