INHIBITION BY SULFOBROMOPHTHALEIN OF MITOCHONDRIAL TRANSLOCATION OF ANIONS AND ADENINE-NUCLEOTIDES - EFFECTS UPON LIVER ADENOSINE-TRIPHOSPHATE AND POSSIBLE CORRELATION WITH INHIBITION OF BILE-FLOW IN RAT

  • 1 January 1976
    • journal article
    • research article
    • Vol. 197  (1) , 235-244
Abstract
Unconjugated sulfobromophthalein (BSP) inhibits state III respiration of rat liver mitochondria. It competitively inhibits the translocation into mitochondria of citrate, malate, phosphate and ADP, as studied by the inhibitor stop method. A double-beam spectrophotometric study strongly suggests that glutamate translocation is similarly inhibited. After perfusion of 65 .mu.mol/h 100 g-1 for 90 min, bile flow is inhibited by 82% and liver ATP falls by 60%. The amount of mitochondrial BSP can be Computed from the amount of [35S]BSP still bound to mitochondria prepared at the end of such experiments; the amount of BSP lost during the isolation procedure is estimated from parallel experiments following binding of BSP in vitro. Comparison of the kinetic constants of mitochondrial transport and of their inhibition by BSP and of liver concentrations of substrates and BSP leads to the conclusion that a strong inhibition of transports, mainly of phosphate, occurs in vivo and is responsible for the observed decrease of ATP levels. The latter is likely to be at least partially responsible for the concomitant decrease in bile flow.