Abstract
In the prereplicative period of regenerating rat liver after a 70% hepatectomy, “the rate of de novo purine synthesis” (“purine synthesis”) increases by 2.4-fold in parallel with plasma glucagon (2.5-fold), hepatic cyclic AMP (cAMP) (2-fold) in the second peak, 5-phosphoribosyl 1-pyrophosphate (PRPP) (3.0-fold) and specific activity of amidophosphoribosyltransferase (ATase) (1.8-fold) (1). Based on these correlations, it was hypothesized that glucagon promotes liver regeneration by increasing “purine synthesis”. To test this hypothesis, the effect of infusion or bolus administration of glucagon or dibutyryl cAMP (Bt2cAMP) was studied in rat liver in regard to “purine synthesis”, ATase activity, concentrations of cAMP, PRPP and purine ribonucleotides. “Purine synthesis” increased (3.5-fold) by infusion for 12 hours (2), but was transiently inhibited by bolus administration (0.5-fold), in spite of increased cAMP (5- vs. 50-fold) and PRPP (1.5- vs. 2.4-fold) concentrations in a dose-dependent and time-dependent manner in both conditions (3). All the other factors were unchanged. These paradoxical effects of glucagon or Bt2cAMP on “purine synthesis” suggest that the mechanism of regulation of “purine synthesis” includes differential phosphorylation of proteins including ATase depending on the difference of magnitude and duration of cAMP increase. (1) Am.J.Physiol. 252, G373, 1986, (2) Am.J.Physiol. 253, E684, 1987, (3) Metabolism, 35, 758, 1986
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Itakura, M., Yamaoka, T., Yoshikawa, H. et al. 63 PARADOXICAL EFFECTS OF GLUCAGON ON DE NOVO PURINE SYNTHESIS IN RAT LIVER. Pediatr Res 24, 121 (1988). https://doi.org/10.1203/00006450-198807000-00087
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DOI: https://doi.org/10.1203/00006450-198807000-00087