PLASMA-MEMBRANE OF THE REGENERATING RAT-LIVER - PLASMA-MEMBRANE AS A KEY TARGET ORGANELLE IN GALACTOSAMINE-INDUCED HEPATITIS

The observation that D-galactosamine-induced hepatitis does not occur in regenerating liver has suggested an experimental system to investigate the factors involved in this form of liver injury. Plasma membranes from regenerating livers, 4 days after partial hepatectomy, and from control rats, that were sham operated, were isolated and the responses to the administration of D-galactosamine were compared. In plasma membranes from regenerating livers, the activity of alkaline phosphatase [EC 3.1.3.1] was increased 5-6-fold and the activity of 5''-nucleotidase [EC 3.1.3.5] was slightly increased, but that of (Na-K)-activated ATPase [EC 3.6.1.3] was the same as in the controls. The incorporation of [14C]L-leucine into plasma membranes from regenerating livers was enhanced by 30%. D-Galactosamine depressed the activities of 5''-nucleotidase and (Na-K)-activated ATPase in the plasma membrane from the controls, but not in regenerating livers. D-Galactosamine reduced the incorporation of [14C]L-leucine in the plasma membranes of control and regenerating livers, though in the latter group to a level that was not significantly below that of the untreated controls. The sphingomyelin content of plasma membranes from the control rats was reduced by D-galactosamine, while that of the regenerating liver was unaffected. [Enzyme activity of glucose-6-phosphatase (EC-3.1.3.9) and succinate dehydrogenase (EC-1.3.99.1) were also studied.] Changes in the plasma membrane play a key role in the indication of galactosamine hepatitis. Lysophosphatidylcholine was increased 4-fold in plasma membrane from regenerating livers, and this increase was suppressed by D-galactosamine. The significance of this observation in relation to the role of lysophosphatidylcholine in membrane fusion is discussed.