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 si ngle pass through a rat liver and replaced in a highly regulated manne r by uridine formed presumably by de novo synthesis. We report a cellu lar basis for the catabolic component of this apparent paradox by diss ociation of the liver with collagenase into two cell fractions, hepato cytes and a nonparenchymal cell population. Suspensions of the nonpare nchymal cells rapidly cleave uridine to uracil, whereas in hepatocytes this activity was <5% of that in nonparenchymal cells. Conversely, he patocytes cause extensive degradation of uracil to p-alanine. These di fferences correlate with the uridine phosphorylase and dihydrouracil d ehydrogenase activity in cell-free extracts of each cell type. We have documented the existence of a Na+-dependent, nitrobenzylthioinosine-i nsensitive transport system for uridine in the parenchymal cells (Mich aelis constant 46 +/- 5 mu M) that achieves a three-to fourfold concen tration gradient in hepatocytes. A similar system is present in the no nparenchymal cell population In addition, a highly specific and active Na+-dependent transport system for beta-alanine, the primary cataboli c metabolite of uracil, has been demonstrated in hepatocytes.