REGULATION OF DNA-POLYMERASE ALPHA ACTIVITY BY THE ALPHA-1-ADRENERGIC RECEPTORS IN PROLIFERATIVELY ACTIVATED RAT-LIVER CELLS

The administration of the α1-adrenergic antagonist prazosin to hepatectomized rats inhibited DNA synthesis induced in the remaining hepatocytes. This inhibitory effect could be reversed by the simultaneous injection of the agonist phenylephrine. In order to establish how the α1-adrenergic receptors can regulate DNA replication, the effect of prazosin administration on DNA polymerase α was examined. At 24 h after partial hepatectomy, the activity of DNA polymerase α increased 5, 7 and 9 fold in the homogenates, nuclei and nuclear matrix, respectively. This increase was inhibited by 70%-80% when prazosin was injected at 1, 8 or 11 h after surgery. Kinetic studies revealed that the Km for DNA was 2 fold lower in hepatectomized than in control animals. The administration of prazosin to hepatectomized rats increased the Km to the control values. These results indicate that the α1-adrenergic receptors are involved in the regulation of DNA synthesis through the activation of DNA polymerase α and that this activation could be produced by increasing its affinity for DNA. © 1991.