Uptake of lipophilic model compounds into the isolated perfused rat epididymal adipose tissue

Uptake of xenobiotics into isolated perfused rat adipose tissue was studied. Aorta and vena cava were cannulated and ligations were placed so that only an epididymal fat pad was perfused. Perfusion experiments were performed in situ and nonrecirculating, for up to 350 min, with Krebs-Ringer bicarbonate buffer containing 4% serum albumin. The functionality of the preparation was tested by an after-perfusion with methylene blue as well as with the volume and mass balances. Formation of edema was not a problem under the experimental conditions used. The following model compounds were used at influx concentrations of 2 to 8 microM: thiopental, imipramine, chlorpromazine, 1,1-bis-(p-chlorophenyl)-2,2-dichloroethane (DDE) and 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB). Uptake was determined during the experiments using the arteriovenous difference and after the experiments by direct determination in the perfused fat pad. All five model compounds were taken up readily. Rate of uptake tended to decrease initially and to reach a constant value. Only with 6-CB was the difference between initial and terminal rate considerable. Mean uptake fraction was: thiopental, 38 +/- 8%; imipramine, 69 +/- 4%; chlorpromazine, 85%; DDE, 56%; and 6-CB, 13 +/- 1%. Thus, imipramine and chlorpromazine, which do not accumulate in adipose tissue in vivo, are even taken up more rapidly into the isolated perfused adipose tissue than is thiopental. The difference between these two experimental situations is therefore not due to a permeability barrier, but rather to factors outside the adipose tissue, such as competing nonadipose tissues present in vivo only. For the neutral, insoluble and almost totally albumin-bound compounds, DDE and 6-CB, albumin may act as an additional binding competitor that inhibits adipose tissue uptake.