TABLE 1

Inhibitory effect of various compounds on the uptake of [3H]digoxin in SCHH lot 109

The uptake of 0.05 μM [3H]digoxin was measured at 37°C for 5 min in the presence and absence of inhibitors. Data are expressed as a percentage of the control values ± S.D. determined using all replicates (n = 3–24) from 1 to 8 experiments. Statistical significance was determined using Student's t test for amiodarone and 500 μM digoxin, whereas all other compounds used the analysis of variance/Dunnett's approach as described under Materials and Methods.

CompoundsInhibitor Concentration[3H]Digoxin Uptake
μM%Control
Control (0.1% DMSO)a100 ± 4.6
Control (1% DMSO)b100 ± 3.1
Control (0.1% MeOH)c100 ± 7.8
OATP substrates/inhibitors
    Cyclosporine A10158 ± 29*
    Rifamycin SV100100 ± 15
    Rifampicin100163 ± 8.6*
    Estrone sulfate10090.5 ± 13
OATP and MCT8 inhibitor
    BSP10096.1 ± 6.6
OATP1B3 Substrate
    CCK-8100100 ± 18
OAT Inhibitors
    PAH500115 ± 13
    Probenecid10089.9 ± 7.3
OCT1 Inhibitor
    Quinidine50103 ± 8.3
Anion transport inhibitor
    DIDS500110 ± 27
Mitochondrial uncouplers
    FCCP5079.2 ± 28
    CCCP5087.4 ± 12
    DNP500114 ± 25
Glucose transporter inhibitor
    Cytochalasin B5093.1 ± 4.8
Flavonoids
    Quercetin5055.4 ± 26*
    Rutin10050.5 ± 4.1*
Cardiac Glycosides
    Digoxin10067.5 ± 14*
    Digoxin (1% DMSO)50045.0 ± 13**
    Ouabain10063.1 ± 2.2*
Antiarrhythmic
    Amiodarone (0.1% MeOH)10097.6 ± 4.6
  • DMSO, dimethyl sulfoxide; PAH, p-aminohippuric acid; DIDS, 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid; CCCP, carbonyl cyanide-m-chlorophenylhydrazone; DNP, 2,4-dinitrophenol.

  • * p < 0.05 and

  • ** p < 0.01, significantly different from control.

  • a The control value was 0.15 pmol/(min · mg protein).

  • b The control value was 0.17 pmol/(min · mg protein).

  • c The control value was 0.12 pmol/(min · mg protein).