HORMONAL-REGULATION OF CONCENTRATIVE NUCLEOSIDE TRANSPORT IN LIVER PARENCHYMAL-CELLS

Na+-dependent uridine uptake is stimulated in isolated rat liver paren chymal cells by glucagon. This effect is transient, reaches maximum le vels of stimulation 10 min after hormone addition, and is dose-depende nt. Glucagon action can be mimicked by agents that are able to hyperpo larize the plasma membrane (e.g. monensin) and by dibutyryl cyclic AMP . The effects triggered by glucagon, monensin and dibutyryl cyclic AMP are not additive, suggesting a common mechanism of action. 8-(4-Chlor ophenylthio)adenosine 3':5'-cyclic monophosphate (PCT), a eye lic AMP analogue, but also a nucleoside analogue, markedly stimulates Na+-depe ndent uridine uptake in an additive manner to that triggered by monens in, similarly to the effect described for nitrobenzylthioinosine. Cons idering the roles reported for nucleosides in liver metabolism, the us e of PCT as a cyclic AMP analogue should be precluded. Insulin is also able to up-regulate Na+-dependent uridine uptake by a mechanism which involves a stable induction of this transport activity at the plasma- membrane level. This is consistent with a mechanism involving synthesi s and insertion of more carriers into the plasma membrane. It is concl uded that the recently characterized hepatic concentrative nucleoside transporter is under short-term hormonal regulation by glucagon, throu gh mechanisms which involve membrane hyperpolarization, and under long -term control by insulin. This is the first report showing hormonal mo dulation of the hepatic concentrative nucleoside transporter.