127 PHOSPHOCREATINE AS A POSSIBLE MODULATOR OF THE ADENYLATE POOL

The administration of purine nucleotide precursors results in a small increase of the adenylate pool because of feedback control mechanisms; nevertheless different tissues have different levels of the adenylate pool. This suggests that other factors may modulate the feedback regulation. We have studied a possible relation between the creatine-phosphocreatine (PC) pool and the adenylate pool and we have determined purine nucleotides, creatine, PC in rat tissues after injection of PC. A significant increase of the creatine-PC pool was observed in those tissues (e.g. myocardiun) in which the creatine-PC pool may freely expand. Adenine and guanine nucleotides were also significantly increased. Even more evident increases were obtained with Raji cell cultures; the creatine-PC pool showed a 5-fold increase (from 1.74 to 20.91 nmoles/106 cells) and the adenylate pool doubled (from 2.91 to 5.25 nmoles/106 cells). Similar results were obtained with hybridctia ascites cells. Both in rat tissues and in cell cultures energy charge was also increased. In cells in which no variation in the creatine and PC levels was observed the adenylate pool was not modified. These results suggest that the creatine-PC pool positively modulate the purine nucleotide pool and explain why tissues with high creatine and PC levels such as heart, muscle, brain, also have a high adenylate pool. It is possible that the increase in the energy charge maintains the adenylate pool at a higher level or that PC decreases the feedback inhibition. Compounds such as exogenous PC that increase the creatine-PC pool seem to be more effective in raising the adenylate pool than nucleotide precursors.