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.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D003597:Cytosine Nucleotides / Q000378:metabolism; D005246:Feedback; D005260:Female; D005688:Galactosamine / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012265:Ribonucleotides / Q000378:metabolism*; D014500:Uracil Nucleotides / Q000378:metabolism; D014529:Uridine / Q000494:pharmacology*; D014532:Uridine Diphosphate Glucose / Q000378:metabolism
D003597:Cytosine Nucleotides; D012265:Ribonucleotides; D014500:Uracil Nucleotides; D005688:Galactosamine; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D014532:Uridine Diphosphate Glucose; D014529:Uridine