Glycogenolytic effect of adenosine involves ATP from hepatocytes and eicosanoids from Kupffer cells.
In the perfused liver, infusion of adenosine (50 microM) caused an increase in portal pressure and glucose output as well as a brief increase in oxygen uptake followed by a transient decrease within 1 min. Half-maximal glycogenolytic effect was observed with approximately 20 microM adenosine, and the stimulation was maximal at concentrations > 50 microM. 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 Kupffer cells participates in the effect of adenosine in the liver. Although adenosine has been reported to increase eicosanoid release from perfused liver (S. vom Dahl, M. Wettstein, W. Gerok, and D. Hüssinger, Biochem. J. 270: 39-44, 1990), in this study adenosine failed to stimulate prostaglandin release from cultured Kupffer cells at concentrations ranging from 1 microM to 1 mM, casting doubt on the hypothesis that Kupffer cells are totally responsible for the effect of adenosine. In contrast, adenosine increased ATP transiently from 4 to 15 nM in effluent from perfused livers concomitant with a transient increase in carbohydrate output and portal pressure. To assess which type of hepatic cells released ATP after addition of adenosine, parenchymal, Kupffer, and endothelial cells were isolated and incubated with adenosine. Adenosine increased ATP concentrations in culture media of parenchymal cells but not from Kupffer or endothelial cells. Furthermore, ATP stimulated prostaglandin release from cultured Kupffer cells, whereas ATP (10 microM) infusion caused glucose release with kinetics similar to adenosine in perfused livers, an effect that was blocked by destroying Kupffer cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Nukina
S
S
Department of Pharmacology, University of North Carolina at Chapel Hill 27599.
Fusaoka
T
T
Thurman
R G
RG
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis / Q000502:physiology*; D005682:Gadolinium / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D066298:In Vitro Techniques; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D010477:Perfusion; D015230:Prostaglandin D2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013929:Thromboxane B2 / Q000096:biosynthesis
D015777:Eicosanoids; D013929:Thromboxane B2; D000255:Adenosine Triphosphate; D006003:Glycogen; D005682:Gadolinium; D005947:Glucose; D000241:Adenosine; D015232:Dinoprostone; C038958:gadolinium chloride; D015230:Prostaglandin D2