GLYCOGENOLYTIC EFFECT OF ADENOSINE INVOLVES ATP FROM HEPATOCYTES AND EICOSANOIDS FROM KUPFFER CELLS

Glycogenolytic effect of adenosine involves ATP from hepatocytes and e icosanoids from Kupffer cells. Am. J. Physiol. 266 (Gastrointest. Live r Physiol. 29): G99-G105, 1944.-In the perfused liver, infusion of ade nosine (50 mu M) caused an increase in portal pressure and glucose out put as well as a brief increase in oxygen uptake followed by a transie nt decrease within 1 min. Half-maximal glycogenolytic effect was obser ved with similar to 20 mu M adenosine, and the stimulation was maximal at concentrations >50 mu M. The effect of adenosine was blocked when Kupffer cells were destroyed with gadolinium chloride treatment (10 mg /kg iv), supporting the hypothesis that eicosanoid release from Kupffe r cells participates in the effect of adenosine in the liver. Although adenosine has been reported to increase eicosanoid release from perfu sed liver (S. vom Dahl, M. Wettstein, W. Gerok, and D. Haussinger, Bio chem. J. 270: 39-44, 1990), in this study adenosine failed to stimulat e prostaglandin release from cultured Kupffer cells at concentrations ranging from 1 mu M to 1 mM, casting doubt on the hypothesis that Kupf fer cells are totally responsible for the effect of adenosine. In cont rast, adenosine increased ATP transiently from 4 to 15 nM in effluent from perfused livers concomitant with a transient increase in carbohyd rate output and portal pressure. To assess which type of hepatic cells released ATP after addition of adenosine, parenchymal, Kupffer, and e ndothelial cells were isolated and incubated with adenosine. Adenosine increased ATP concentrations in culture media of parenchymal cells bu t not from Kupffer or endothelial cells. Furthermore, ATP stimulated p rostaglandin release from cultured Kupffer cells, whereas ATP (10 mu M ) infusion caused glucose release with kinetics similar to adenosine i n perfused livers, an effect that was blocked by destroying Kupffer ce lls. These data are consistent with the hypothesis that stimulation of parenchymal cell glycogenolysis by adenosine involves release of ATP from parenchymal cells and stimulation of eicosanoid release from Kupf fer cells that activate glycogenolysis in parenchymal cells.