Uridine catabolism in Kupffer cells, endothelial cells, and hepatocytes

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Abstract
Kupffer cells, endothelial cells, and hepatocytes from rats were separated by centrifugal elutriation. The rate of uracil formation from [2-14C]uridine, the 1st step in uridine catabolism, was monitored in suspensions of the 3 different liver cell types. Kupffer cells demonstrated the highest rate of uridine phosphorolysis, 15 min after the addition of the nucleoside the label in uracil amounted to 51%, 13% and 19% of total radioactivity in the medium of Kupffer cells, endothelial cells, and hepatocytes, respectively. If corrected for Kupffer cell contamination, hepatocyte suspensions demonstrated activities similar to endothelial cells. Hepatocytes continuously cleared uracil from the incubation medium. The lack of uracil consumption by Kupffer cells and endothelial cells pointed to uracil as the end-product of uridine catabolism in these cells. Kupffer cells and endothelial cells did not produce radioactive CO2 upon incubation in the presence of [2-14C]uridine. Hepatocytes, were able to degrade uridine into CO2, .beta.-alanine and ammonia as demonstrated by active formation of volatile radioactivity from the labeled nucleoside. There was almost no detectable formation of thymidine or of cytosine, uracil or uridine from cytidine by any of the different cell types tested. These results are in line with low thymidine phosphorolysis and cytidine deamination in rat liver. A co-operation of Kupffer cells, endothelial cells and hepatocytes is suggested in the breakdown of uridine from portal vein blood with uridine phosphorolysis occurring in the Kupffer cells and with uracil catabolism restricted to parenchymal liver cells.