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 mumol/min per g of liver). Addition of adenosine (150 microM) 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 Pi, 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 Pi: 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 Pi and of glycogenolysis. The fate of the cytosolic Pi was unclear, especially with administered ATP, which did not increase the n.m.r.-detectable intracellular ATP.
Vanstapel
F
F
Biomedische NMR Eenheid, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Belgium.
Waebens
M
M
Van Hecke
P
P
Decanniere
C
C
Stalmans
W
W
D000241:Adenosine / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002451:Cell Compartmentation; D015777:Eicosanoids / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D010101:Oxygen Consumption; D010710:Phosphates / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D011983:Receptors, Purinergic / Q000502:physiology
D015777:Eicosanoids; D008112:Liver Glycogen; D010710:Phosphates; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D006005:Phosphorylases; D000241:Adenosine