Table 1

Ligand specificities of CAR and PXR with selected xenobiotics

GAL4-LBD Fusion
LigandConcentrationmCARmCAR +1 μM ANDRhCARhCAR +10 μM EE2mPXRhPXR
DMSO or ethanol0.1%1.00  ±  0.051.00  ±  0.081.00  ±  0.071.00  ±  0.081.00  ±  0.051.00  ±  0.08
TCPOBOP0.5  μM2.30  ±  0.12 1-a 12.52  ±  1.20 a 0.90  ±  0.101.05  ±  0.130.92  ±  0.041.70  ±  0.15  a
ANDR10  μM0.08  ±  0.01 1-a N.D.0.70  ±  0.11 a N.D.0.97  ±  0.071.41  ±  0.12  a
EE210  μM1.68  ±  0.15  1-a 8.18  ±  0.23 a 0.41  ±  0.05 a N.D.1.14  ±  0.061.97  ±  0.02  a
5β-Pregnanedione10  μM0.20  ±  0.07 1-a N.D.1.50  ±  0.13 a 1.83  ±  0.23  a 1.73  ±  0.06  a 2.26  ±  0.23  a
RU48610  μM0.86  ±  0.030.99  ±  0.150.82  ±  0.121.03  ±  0.093.52  ±  0.34 1-a 3.21  ±  0.58  a
RIF10  μM0.99  ±  0.080.95  ±  0.100.98  ±  0.231.02  ±  0.190.85  ±  0.074.56  ±  0.47  1-a
CLOTR2  μM1.30  ±  0.213.79  ±  0.44  1-a 2.19  ±  0.03  a 4.02  ±  0.05 a 2.28  ±  0.32  a 2.70  ±  0.15  a

Data are expressed as mean ± S.D. (n = 3) of fold activation of normalized luciferase activity. Other NR ligands (WY-14643, arotinoic acid, 25OH-cholesterol, VD3, and T3) were without any significant effect (≤ 15%) on hCAR or mCAR. Only chenodeoxycholic acid was a weak reactivator of ANDR-suppressed mCAR (2-fold). ANDR and EE2 did not have significant effects on VDR-, PPARα-, or FXR-dependent activities.

    • N.D., not done.

    • ↵1-a Statistically different from vehicle (p < 0.05).