CORRELATION BETWEEN CELLULAR ATP LEVEL AND BILE EXCRETION IN THE RAT LIVER

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Abstract
The influence of the cellular level of ATP in the liver on bile excretion was studied in rats. In ischemia, the cellular ATP level decreased rapidly and, concomitantly, bile flow stopped within 5 min. Administration of L-ethionine i.p. to rats reduced the bile flow rate with decrease in the cellular ATP level. The correlation between the bile flow rate and the cellular ATP level was confirmed in a liver perfusion system. On anoxic perfusion, the ATP level and bile flow rate changed in the same manner as in ischemia. The recovery rates of both on reoxygenation decreased with increase in the anoxic perfusion period. During perfusion under oxygenated conditions, decrease in cellular ATP to various levels by infusion of various concentrations of KCN, an inhibitor of respiration, resulted in corresponding and concomitant suppression of bile excetion. Kinetic analysis of the bile flow rate revealed a Michaelis-Menten-type curve for the cellular ATP level. The apparent Km for ATP of bile flow rate in L-ethionine-treated rat liver and liver perfused with KCN were 1.0 and 1.6 mM, and their Vmax values were 4.1 and 2.5 .mu.l/min per g liver, respectively. The concentrations of main bile components, such as phospholipids, cholesterol and taurocholate increased, but their total outputs decreased with decrease in the ATP level, and returned to the normal range with recovery of the ATP level. Thus, it was shown experimentally that the extent of hepatic injury can be assessed simply by monitoring the bile flow rate, which reflects the cellular level of ATP.