MODULATION OF MAXIMAL GLYCOGENOLYSIS IN PERFUSED-RAT-LIVER BY ADENOSINE AND ATP

Rat livers perfused at constant flow via the portal vein with dibutyryl cyclic AMP produced glucose equivalents at a steady maximal rate (6-mu-mol/min per g of liver). Addition of adenosine (150-mu-M) caused a biphasic effect. (i) First, the glycogenolytic rate rose transiently, to a mean peak of 150 % of control levels after 2 min. This glycogenolytic burst was reproduced by two P1-receptor agonists, but not by ATP, and was blocked by a P1-antagonist (8-phenyltheophylline), as well as by inhibitors of eicosanoid synthesis (indomethacin, ibuprofen or aspirin). It did not occur in phosphorylase-kinase-deficient livers. The adenosine-induced glycogenolytic burst coincided with moderate and transient changes in portal pressure (+6 cmH2O) and O2 consumption (-20 %), but it could not be explained by an increase in cytosolic P(i), since the n.m.r. signal fell precipitously. (ii) Subsequently, the rate of glycogenolysis decreased to one-third of the preadenosine value, in spite of persistent maximal activation of phosphorylase. The decrease could be linked to the decline in cytosolic P(i): both changes were prevented by the adenosine kinase inhibitor 5-iodotubercidin, whereas they were not affected by ibuprofen or 8-phenyltheophylline, and were not reproduced by non-metabolized adenosine analogues. In comparison with adenosine, ATP caused a slower decrease of P(i) and of glycogenolysis. The fate of the cytosolic P(i) was unclear, especially with administered ATP, which did not increase the n.m.r.-detectable intracellular ATP.