1. The effect of pretreatment of rats with the peroxisome proliferator 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) on sulphobromophthalein excretion from the isolated perfused rat liver has been investigated and compared with the effect of clofibrate which is also a peroxisome proliferator. 2. Rats fed 2,4,5-T at a dose of 0.25% in the diet showed a decrease in food intake, compared with controls and clofibrate-fed rats. 3. Treatment with either 2,4,5-T or clofibrate was associated with significant inhibition of the biliary excretion of unchanged, conjugated, and total sulphobromophthalein from perfused rat liver, compared with diet-matched controls. 4. There was a decrease in bile flow in the clofibrate-treated group, but not in the 2,4,5-T-treated group. 5. The results of the present study confirm previous studies that have shown an association between peroxisome proliferation treatment and inhibition of glutathione S-transferase-mediated sulphobromophthalein excretion.

1. Ethacrynic acid (EA), a phenoxyacetic acid diuretic, has similar effects to tienilic acid (TA) on rat liver glutathione S-transferase (GST) activity in vitro, using either 1-chloro-2,4-dinitrobenzene or sulphobromophthalein (BSP) as a substrate. EA inhibits the basic rat liver GST, with inhibition being greater with GST containing subunits 3 and 4 than with those containing subunits 1 and 2. 2. In vitro inhibitors of GST can inhibit biliary excretion of BSP in a perfused liver. 3. A single bolus dose of EA had no effect on BSP excretion from the isolated perfused rat liver, and this is most likely due to the rapid disappearance of EA from the perfusion media. Experiments using perfused rat liver indicated that a sustained high concentration of EA in the perfusion media has an inhibitory effect on the excretion of both unchanged and conjugated BSP. 4. A decrease in BSP excretion may not be an indicator of liver damage, but a consequence of GST inhibition.

Previous studies from this labOl:atory have implicated the sympathetic neurotransmitter noradrenaline (NA) in regulation of woolft'_z The current study was undertaken to investigate [3H]NA accumulation and its localization by Merino skin, and to determine the effects of gonadal and glucocorticoid steroids on such uptake.The presence of an active uptake system was demonstrated and the process was partially characterized in terms of its magnitude, time course, concentration dependence and requirement for various nutrient and ionic factors. The uptake was seen to occur predominantly into cocaine-and 6-hydroxydopamine-sensitive sites in skin from various body regions of Merino sheep. None of three steroids tested in vivo or in vitro was seen to influence the uptake process.These results do not enable us to correlate the observed [3H]NA uptake process with the previously reported effects of NA on wool growth.