Adenosine Induces System A Amino Acid Transport in Cultured Rat

Adenosine caused a 2.5-fold increase in the sodium-dependent uptake of 2-aminoisobutyric acid in rat hepatocytes in primary culture following incubation for 3h. The range of stimulating concentrations of adenosine corresponded to that of cAMP formation. Adeno-sine increased the Fmax of the transport without altering the Ka for 2-aminoisobutyric acid. These effects of adenosine were abolished by actinomycin D. iV'-L-Phenylisopropyladeno-sine also caused twofold increase in the amino acid transport. These findings suggest that adenosine induces System A amino acid transport in a transcription-dependent manner, and that Pi-purinergic receptors are mainly involved in this action of the nucleoside. A-The available data suggest that adenosine can modulate the intracellular metabolism of various tissues including the liver (2). Due to the production and elimination of adeno-sine by parenchymal and nonparenchymal liver cells (2), the blood levels of this nucleoside are changed during intrahepatic circulation. Liver cells possess both Pi- and P2-purinergic receptors on the plasma membrane, which are involved in many metabolic actions of adenosine (3). The nucleoside has been shown to increase the output of glucose and the formation of urea in perfused liver and in isolated hepatocytes (4-6). However, it has not been determined whether adenosine regulates the availability of the metabolic precursors such as amino acids or trioses. In this paper, we demonstrate that adenosine induces System A transport of amino acids in cultured rat hepatocytes mainly through the Pi-purinergic receptors