Table 4

Uptake of [3H]ISIS-9389 by liver cell types

Cell TypeContribution to Total Liver Uptake4-a4-b4-eAdministered Dose in Cell Type4-a4-c4-eTotal Cellular Load4-a4-d4-e
% μM
Parenchymal cells24.9  ± 7.721.8  ± 6.71.5  ± 0.5
Kupffer cells23.3  ± 2.520.4  ± 2.251.5  ± 5.5
Endothelial cells51.9  ± 6.445.5  ± 5.686.1  ± 10.6
  • 4-a  Rats were injected with [3H]ISIS-9389 (1 mg/kg of body weight). Sixty minutes later, parenchymal, Kupffer, and endothelial cells were isolated, and the association of radioactivity to each cell type was determined.

  • 4-b  Contribution of each cell type to the total liver uptake was calculated from the uptake per milligram of cell protein and the contribution of each cell type to the total liver protein (Nagelkerke et al., 1983).

  • 4-c  Percentage of the administered dose taken up by each cell type (when all oligonucleotide is cleared) was calculated from the contribution of the cells to the total liver uptake and the contribution of the liver to the clearance of ISIS-9389 (87.7 ± 0.8%).

  • 4-d  Total cellular loads (intracellular concentrations reached when all oligonucleotide is cleared) were calculated from the sizes of the different cellular compartments (details under Materials and Methods).

  • 4-e  Values are means ± S.E.M. of four rats.