TABLE 1

The kinetics of PAH transport by OAT1 in the absence versus presence of inhibitors

The concentration of inhibitor drug used is indicated in the parentheses. The inhibitor concentrations used were fixed at a concentration expected to inhibit ∼50%–75% of transport activity. The concentrations were based on previously determined inhibitory concentration 50 (IC50) values (Ingraham et al., 2014), or were determined in preliminary experiments. Data are mean ± S.E.M. of four to five experiments.

JmaxKmInhibition Mechanism
pmol ⋅ mg protein−1 ⋅ min−1μM
Control1095 ± 26922.3 ± 2.4
Probenecid (15 μM)897 ± 23342.0 ± 4.8aCompetitive
Control1095 ± 17214.8 ± 2.1
Cidofovir (100 μM)1388 ± 37350.1 ± 17.6aCompetitive
Control759 ± 88.014.5 ± 1.1
Ibuprofen (5 μM)1057 ± 93.849.3 ± 5.4bCompetitive
Control632 ± 80.415.1 ± 2.8
Estrone-3-sulfate (250 μM)620 ± 78.657.9 ± 9.5aCompetitive
Control939 ± 14521.9 ± 3.9
Indomethacin (5 μM)921 ± 17451.3 ± 15aCompetitive
Control733 ± 13319.0 ± 2.2
Furosemide (30 μM)710 ± 13838.5 ± 5.0aCompetitive
Control762 ± 14719.2 ± 2.0
Morin (15 μM)684 ± 11372.5 ± 6.8bCompetitive
Control945 ± 20.917.6 ± 3.4
Pravastatin (1000 μM)1043 ± 13048.8 ± 13.8cCompetitive
Control828 ± 81.214.8 ± 1.5
Valsartan (15 μM)637 ± 13839.7 ± 6.8aCompetitive
Control721 ± 11313.3 ± 0.95
Olmesartan (15 μM)801 ± 11477.6 ± 12bCompetitive
Control518 ± 42.129.6 ± 6.1
Telmisartan (0.5 μM)121 ± 9.1b37.3 ± 6.9Noncompetitive
Control1083 ± 71.717.3 ± 2.7
Azilsartan (15 μM)833 ± 68.2c27 ± 5.3Noncompetitive
Control933 ± 76.916.8 ± 2.7
Irbesartan (10 μM)574 ± 65.8c31.8 ± 5.3cMixed-type
Control921 ± 60.415.5 ± 1.5
Omeprazole (20 μM)698 ± 47.7c37.0 ± 3.8bMixed-type

  • ↵a P < 0.01, statistically significantly different versus control, two-tailed Student’s t test.

  • ↵b P < 0.001, statistically significantly different versus control, two-tailed Student’s t test.

  • ↵c P < 0.05, statistically significantly different versus control, two-tailed Student’s t test.