Human adult and foetal liver sulphotransferases: inhibition by mefenamic acid and salicylic acid

1. The aim was to see whether mefenamic acid and salicylic acid had differe nt inhibition profiles for SULT1A1 (substrate: 4-nitrophenol) and SULT1A3 ( dopamine) activities and on (-)-salbutamol and minoxidil sulphation rates i n the human adult and mid-gestational foetal livers. 2. The activity (pmol min(-1) mg(-1)) of SULT1A1 was 662 +/- 78 (adult) and 246 +/- 159 (foetus; p = 0.0003) and that of SULT1A3 was 24 +/- 4 (adult) and 121 +/- 90 (foetus; p = 0.030). The rate (pmol min 1 mg 1) of (-)-salbu tamol sulphation was 109 +/- 27 (adult) and 117 +/- 34 (foetus; p = 0.144) and that of minoxidil sulphation was 202 +/- 38 (adult) and 108 +/- 44 (foe tus; p = 0.001). 3. With mefenamic acid as an inhibitor, the IC50 (mm) for SULT1A1 was 0.02 +/- 0.004 (adult) and 0.01 +/- 0.002 (foetus; p = 0.001); for SULT1A3 it wa s 76 +/- 6 (adult) and 77 +/- 13 (foetus; p = 0.889); for the rate of (-)-s albutamol sulphation it was 0.07 +/- 0.005 (adult) and not determinable (fo etus) and for minoxidil sulphation it was 1.6 +/- 0.7 (adult) and 0.15 +/- 0.04 (foetus; p = 0.076). 4. With salicylic acid as an inhibitor, the IC50 (muM) for SULT1A1 was 30 /- 2 (adult) and 25 +/- 1 (foetus; p = 0.011); for SULT1A3 it was 690 +/- 3 6 (adult) and 570 +/- 16 (foetus; p = 0.229); for the rate of (-)- salbutam ol sulphation it was 93 +/- 11 (adult) and 344 +/- 42 (foetus; p = 0.010); with minoxidil as substrate, the IC50 was not determinable. 5. In summary, SULT1A1, SULT1A3 and the sulphotransferases towards (-)-salb utamol and minoxidil had measurable activities in the mid-gestational human foetal liver. Mefenamic acid was a more potent inhibitor than salicylic ac id of both human adult and foetal liver SULT1A1 and SULT1A3 activities. Foe tal liver SULT1A1 was more susceptible than adult liver SULT1A1 to inhibiti on by mefenamic acid and salicylic acid. These results are consistent with the view that sulphotransferases develop early in the human foetal liver an d drugs may inhibit their activities.