Table 3

Effects of various inhibitors and hypothermia on uptake of ONO-1301, and effects of ONO-1301 on the uptake of TCA and pravastatin by isolated rat hepatocytes3-a

Uptake
Na+-dependent (%)3-aNa+-independent (%)3-a
ONO-1301 uptake
 Control100100
 O°C1.2  ± 1.2***3-b 5.0  ± 1.6***3-b
 Rotenone, 30 μM51.5  ± 17.247.4  ± 1.8***3-b
 FCCP, 2 μM82.2  ± 27.934.3  ± 2.2***3-b
 ONO-1301 500 μM13.4  ± 7.2***3-b 4.0  ± 1.4***3-b
 TCA, 20 μM64.2  ± 17.7*3-b 78.4  ± 3.2
 TCA, 50 μM109.4  ± 65.753.1  ± 5.6***3-b
 TCA, 100 μM71.4  ± 18.950.0  ± 2.7***3-b
 TCA, 500 μM23.4  ± 11.8***3-b 44.3  ± 3.9***3-b
 Pravastatin, 20 μM33.9  ± 14.2**3-b 95.1  ± 4.9
 Pravastatin, 50 μM51.3  ± 15.7*3-b 74.1  ± 3.1*3-b
 Pravastatin, 100 μM44.4  ± 20.6**3-b 67.6  ± 2.6**3-b
 Pravastatin, 500 μM49.4  ± 19.4*3-b 45.5  ± 2.8***3-b
Pravastatin uptake
 Control100
 Pravastatin, 500 μM16.8  ± 1.1***3-b
 ONO-1301, 1 μM87.1  ± 4.1
 ONO-1301, 10 μM40.3  ± 3.1***3-b
 ONO-1301, 100 μM6.5  ± 1.1***3-b
 ONO-1301, 500 μM4.6  ± 2.0***3-b
TCA uptake
 Control100100
 TCA, 500 μM4.3  ± 0.6***3-b 6.9  ± 3.3***3-b
 ONO-1301, 1 μM90.2  ± 4.095.6  ± 13.5
 ONO-1301, 10 μM44.7  ± 3.5*3-b 60.4  ± 6.1*3-b
 ONO-1301, 100 μM9.2  ± 1.8***3-b 28.8  ± 5.2***3-b
 ONO-1301, 500 μM2.5  ± 0.7***3-b 19.2  ± 3.3***3-b
  • 3-a Each value represents the mean ± S.E. of six determinations in two different preparations.

  • 3-b Statistically significant (analysis of variance), * P < .05, ** P < .01, *** P < 0.001 vs.control.