Table 2. Uptake of [³H]ISIS-9388 and [³H]ISIS-3082 by liver cell types.

Oligonucleotide	Cell type	ng/mg of cell protein (at 60 min)	Total cellular load (µM)	Uptake index (µl/h/mg protein)	% of total liver uptake
ISIS-9388	Parenchymal cells	33.7 ± 6.5	1.9 ± 0.3	2.7 ± 0.5a	33.0 ± 5.9
	Kupffer cells	660.3 ± 19.6	47.2 ± 9.5	66.8 ± 13.4b	21.3 ± 2.6
	Endothelial cells	1260.0 ± 286.9	76.3 ± 11.3	108.0 ± 16.0a	45.7 ± 5.6
ISIS-3082	Parenchymal cells	23.0 ± 3.8	1.1 ± 0.2	3.3 ± 0.5	39.6 ± 4.5
	Kupffer cells	90.0 ± 33.8	4.4 ± 1.6	12.8 ± 4.8	4.3 ± 1.7
	Endothelial cells	901.0 ± 7.5	43.6 ± 0.4	128.7 ± 1.1	56.1 ± 3.0

Rats were injected with [³H]ISIS-9388 or [³H]ISIS-3082 (1 mg/kg body wt). Sixty minutes later, parenchymal, endothelial and Kupffer cells were isolated and the cell-associated radioactivity was determined. The amount of oligonucleotide found in each cell type is given per mg cell protein. Total cellular loads (intracellular concentrations reached when all oligonucleotide had been cleared) were calculated by extrapolaton from the amounts of oligonucleotide in the liver at 60 min after injection, taking into account a hepatic cellular protein content of 17.7 ± 1.4% (mean ± SEM of seven determinations) and assuming that 75% of the cellular volume consists of water. Uptake indices (µl plasma cleared/h/mg cell protein) were calculated as described earlier (43). Differences in the uptake indices of ISIS-9388 and ISIS-3082 were tested for significance using Wilcoxon’s two-sample test (44) (^anot significant; ^bP < 0.05). The contribution of each cell type to total liver uptake was calculated from the uptake per mg cell protein and the contribution of each cell type to total liver protein. Values are means ± SEM of three or four rats.