Induction of cytochrome P4501A by smoking or omeprazole in comparison with UDP-glucuronosyltransferase in biopsies of human duodenal mucosa.
Drug-metabolizing enzymes were investigated in duodenal biopsy specimens. Cytochrome P4501A (CYP1A) activity was determined by measuring 7-ethoxyresorufin O-deethylase (EROD) activity in biopsies from 20 smokers (3-30 cigarettes per day), 21 nonsmokers, and 10 nonsmokers receiving omeprazole treatment (20-60 mg/day for at least 1 week). Omeprazole is known to act as a polycyclic aromatic hydrocarbon (PAH)-type inducer in humans. EROD activity was found to be significantly induced in smokers and omeprazole-treated patients, with medians of 2.1 and 1.1 pmol.min-1.mg protein-1, respectively, compared with 0.5 pmol.min-1.mg protein-1 in nonsmokers. Immunoblot analysis substantiated that EROD activity was correlated with CYP1A protein. In contrast, UDP-glucuronosyltransferase (UGT) activity towards 4-methylumbelliferone (an overlapping substrate of several constitutive and inducible UGTs) was not significantly affected. The results demonstrate CYP1A induction by omeprazole and by constituents of cigarette smoke in the human duodenum and support the utility of duodenal biopsies to monitor CYP1A induction by PAH-type inducers.
Buchthal
J
J
Institute of Toxicology, University of Tübingen, Germany.
Grund
K E
KE
Buchmann
A
A
Schrenk
D
D
Beaune
P
P
Bock
K W
KW
D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004386:Duodenum / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000201:enzymology; D009853:Omeprazole / Q000494:pharmacology*; D010088:Oxidoreductases / Q000096:biosynthesis*; D012907:Smoking / Q000378:metabolism*
D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D014453:Glucuronosyltransferase; D009853:Omeprazole