Dibutyryl Cyclic AMP Enhances the Down-Regulation of RB Protein During G1 Phase in the Proliferating Primary Rat Hepatocytes, but Inhibits Their Entries into S Phase and RB′s Phosphorylation

Abstract

To elucidate the cAMP′s bi-directional dual effect on hepatic regeneration with a special reference to RB protein, we studied the serial change of RB protein in the proliferating primary rat hepatocytes and the effect of dibutyryl cAMP (DBcAMP) on it. RB protein in the hepatocytes was down-regulated during the G1 phase, and the highly phosphorylated / the underphosphorylated ratio of RB protein increased at the S phase. DBcAMP (1mM) addition, inhibitory on the DNA synthesis, enhanced this down-regulation, but did not increase the phosphorylated form of RB protein at the S phase. High dose of cAMP at the late G1-G1/S phase could block some essential events for G1/S transition including phosphorylation of RB protein.