Response of isolated rat hepatocytes to D-galactosamine and uridine

Isolated rat hepatocytes preserved for several hours their contents of ATP, CTP, GTP, UTP and UDPG. Leakage of intracellular and membrane-bound enzymes remained in the range observed with the isolated perfused rat liver. D-Galactosamine led to a rapid decrease of the UTP and UDPG contents while ATP and GTP levels remained unaffected. The sum of acid-soluble uracil nucleotides increased immediately after the addition of D-galactosamine, indicating release of the UTP-mediated feed-back inhibition of pyrimidine nucleotide de novo biosynthesis. Addition of uridine to a hepatocyte suspension resulted in a rapid increase in the levels of uridylate derivatives; the concentrations of UTP and UDPG, previously depleted by D-galactosamine, were restored within 1 h. Isolated hepatocytes appear suitable for studies on the pathogenic sequence of events elicited by D-galactosamine and on the regulation of pyrimidine biosynthesis.