Differential inhibition of human liver and duodenum sulphotransferase activities by quercetin, a flavonoid present in vegetables, fruit and wine.
1. Quercetin is a natural flavonoid present in vegetables, fruit and wine, and is known to inhibit sulphotransferase. Drugs are often taken orally and the intestinal mucosa is an early site of drug metabolism. The aims of this investigation were to study the inhibition of dopamine, (-)-salbutamol, minoxidil and paracetamol sulphation by quercetin in the duodenal mucosa and liver and to compare the IC50 in these tissues. 2. The rates (pmol min(-1) mg(-1)) of sulphation of 4-nitrophenol were 343+/-92 (liver) and 164+/-22 (duodenum; p = 0.031), of dopamine were 15+/-11 (liver) and 656+/-516 (duodenum; p = 0.049), of (-)-salbutamol 153+/-31 (liver) and 654+/-277 (duodenum; p = 0.018), of minoxidil were 156+/-47 (liver) and 105+/-7 (duodenum; n.s.), and of paracetamol were 229+/-86 (liver) and 328+/-187 (duodenum; n.s.). 3. The IC50 of quercetin for 4-nitrophenol was 48+/-11 nM (liver) and 56+/-1 nM (duodenum, n.s.), for dopamine was 5.7+/-0.7 microM (liver) and 170+/-12 microM (duodenum, p < 0.0001), for (-)-salbutamol was 54+/-4 nM (liver) and 16+/-8 microM (duodenum; p = 0.025), for minoxidil was 134+/-22 nM (liver) and 3+/-0.3 microM (duodenum, p = 0.013), and for paracetamol was 57+/-7 nM (liver) and 35+/-1 microM (duodenum; p = 0.0002). 4. Quercetin inhibited the sulphation of 4-nitrophenol, dopamine, (-)-salbutamol, minoxidil and paracetamol both in liver and duodenum. With dopamine, (-)-salbutamol, minoxidil and paracetamol as substrates, quercetin was a more potent inhibitor in the liver than the duodenum. Such a difference may reflect the different composition of sulphotransferase forms in the liver and duodenum.
Marchetti
F
F
Department of Neurosciences, Section of Pharmacology, Medical School, Pisa, Italy.
De Santi
C
C
Vietri
M
M
Pietrabissa
A
A
Spisni
R
R
Mosca
F
F
Pacifici
G M
GM
D000082:Acetaminophen / Q000494:pharmacology; D000368:Aged; D000420:Albuterol / Q000494:pharmacology; D001682:Biological Availability; D004298:Dopamine / Q000494:pharmacology; D004347:Drug Interactions; D004386:Duodenum / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D005638:Fruit; D006801:Humans; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D008914:Minoxidil / Q000494:pharmacology; D011794:Quercetin / Q000493:pharmacokinetics / Q000494:pharmacology*; D015238:Sulfotransferases / Q000037:antagonists & inhibitors*; D014675:Vegetables; D014920:Wine
D000082:Acetaminophen; D008914:Minoxidil; D011794:Quercetin; D015238:Sulfotransferases; D000420:Albuterol; D004298:Dopamine