Discrete roles of hepatocytes and nonparenchymal cells in uridine catabolism as a component of its homeostasis.

Previous studies indicated that uridine is essentially cleared in a single pass through a rat liver and replaced in a highly regulated manner by uridine formed presumably by de novo synthesis. We report a cellular basis for the catabolic component of this apparent paradox by dissociation of the liver with collagenase into two cell fractions, hepatocytes and a nonparenchymal cell population. Suspensions of the nonparenchymal cells rapidly cleave uridine to uracil, whereas in hepatocytes this activity was <5% of that in nonparenchymal cells. Conversely, hepatocytes cause extensive degradation of uracil to β-alanine. These differences correlate with the uridine phosphorylase and dihydrouracil dehydrogenase activity in cell-free extracts of each cell type. We have documented the existence of a Na+-dependent, nitrobenzylthioinosine-insensitive transport system for uridine in the parenchymal cells (Michaelis constant 46 ± 5 μM) that achieves a three- to fourfold concentration gradient in hepatocytes. A similar system is present in the nonparenchymal cell population. In addition, a highly specific and active Na+-dependent transport system for β-alanine, the primary catabolic metabolite of uracil, has been demonstrated in hepatocytes.