Effect of lead on calcium-mediated cell function in the isolated rat hepatocyte

The effect of lead on the regulation of pyruvate kinase by glucagon and epinephrine was studied in the isolated rat hepatocyte in primary cell culture. Hepatocytes were incubated in medium containing 0, 10, 50, or 100 μ m Pb 2+. After 20 hr exposure to lead, the cells were stimulated with 1 μ m glucagon or 10 μ m epinephrine, and the activity of pyruvate kinase was measured from 0 to 90 min. The cytotoxicity of lead was evaluated by monitoring the incorporation of radiolabeled precursors into protein and RNA. Incubation in concentrations up to 100 μ m lead acetate for up to 24 hr did not impair protein or RNA synthesis. Return to basal levels of pyruvate kinase activity was delayed or inhibited in lead-intoxicated hepatocytes following epinephrine stimulus but not glucagon, although the unstimulated level of pyruvate kinase and the magnitude of inactivation by the hormones were not affected by lead intoxication. The present study provides evidence that a cell function mediated by Ca 2+ ions as a second messenger is affected by lead intoxication.