Effect of adenosine on the adenine nucleotide content and metabolism of hepatocytes.

ADENOSINE (0.5 MM) added to hepatocyte suspensions increased the intracellular concentration of ATP and total adenine nucleotides within 60 min up to three-fold. 2. Adenosine at 0.5 mM inhibited gluconeogenesis from lactate by about 50%. At higher adenosine concentrations the inhibition was less. There was no strict parallelism between the time-course of the increase of the adenine nucleotide content and the time-course of the inhibition of gluconeogenesis from lactate. 3. Adenosine abolished the accelerating effects of oleate and dibutyryl cyclic AMP on gluconeogenesis from lactate. 4. Gluconeogenesis was no significant effect of adenosine with fructose, dihydroxyacetone or glycerol. With asparagine, adenosine caused anacceleration of glucose formation. 5. Adenosine incorporation into adenine nucleotides accounted for about 20% of the adenosine removal. 6. Inosine, hypoxanthine or adenine compared with adenosine gave relatively slight increases of adenine nucleotides. 7. Urea synthesis from NH4Cl under optimum conditions i.e. in the presence of ornithine, lactate and oleate, was also inhibited by adenosine. The inhibition increased with the adenosine concentration and was 65% at 4 mM-adenosine. Again there was no correlation between the degree of inhibition of urea synthesis and the increase in the adenine nucleotide content. 8. The basal O2 consumption, the increased O2 consumption on the addition of oleate and the rate of formation of ketone bodies were not affected by the addition of adenosine. The [beta-hydroxybutyrate]/[acetoacetate] ratio was increased by adenosine, provided that lactate was present. 9. The increase of the adenine nucleotide content of the hepatocytes on the addition of adenosine may be explained on the assumption that adenosine kinase is not regulated by feedback but by substrate supply.