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The effects of a number of hepatotoxic and other agents on the ATP content of rat liver are described. Changes in the distribution of ATP between the cell sap and the large-particle fraction were determined at intervals after rats had been dosed with various substances. Ethionine produced a rapid decrease in total liver ATP but no alteration in its intracellular distribution. Carbon tetrachloride, sodium salicylate, dimethylnitrosamine, 2,4-dinitrophenol, icterogenin, sodium succinate, sodium malonate and sodium taurocholate did not significantly alter the total ATP content of liver in the periods studied but changes in intracellular distribution were found. Carbon tetrachloride, malonate and taurocholate decreased, and salicylate treatment increased, the proportion of ATP in the cell sap. Treatment with sodium phenobarbitone increased the total liver ATP and the total amount of ATP in the cell sap. The changes in ATP concentration and in the intracellular distribution of ATP are correlated with changes previously reported in bile flow (Delaney &amp; Slater, 1969). No general correlation was found between changes in total ATP and changes in bile flow rate, but there was a relationship between changes in bile flow and in ATP content in the case of ethionine. With the exception of taurocholate and icterogenin, which possibly act on a membrane site, an approximate correlation was found between changes in bile flow and changes in the amount of ATP in the cell sap. The findings are discussed in terms of possible mechanisms for biliary secretion.

Liver adenosine triphosphate content and bile flow rate in the rat