title: Individual metabolic capacity evaluation of cytochrome P450 2C19 by protein and activity in the small intestinal mucosa of Japanese pancreatoduodenectomy patients.
abstract: Some P450 enzymes are expressed not only in the liver but also in the small intestine, and these enzymes play an important role in first-pass drug metabolism in the small intestine. Cytochrome P450 (CYP)2C19 has been confirmed to exist in the small intestine of white people, but not yet in Japanese. We investigated the mRNA level, protein level, and activity of CYP2C19 in the small intestine in a Japanese population. Samples were obtained from the healthy portions of resected small intestines from 18 patients who had undergone pancreatoduodenectomy. The microsomes were extracted from the epithelium of the small intestinal tissues. CYP2C19 mRNA and protein levels were analyzed using real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. CYP2C19 activity in the microsomes was evaluated based on the 5-hydroxylation of lansoprazole using HPLC. CYP2C19 mRNA and protein levels and activities in the small intestine showed interindividual differences. CYP2C19 mRNA levels were not correlated with protein levels or its activity. On the other hand, there was significant correlation between CYP2C19 protein levels and its activity. Further, CYP2C19 protein levels and activities in the small intestine were approximately equal to those in liver. These results suggest the metabolic capacity of CYP2C19 in Japanese small intestine may play as important a role as the liver in drug metabolism. Analyses of the protein level or protein activity of CYP2C19 rather than its mRNA level should be required for predicting the individual metabolic capacity of CYP2C19 in the small intestine.
authors.affiliation: Department of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216–8511, Japan. mikihito-hayashi@marianna-u.ac.jp
authors.forename: Mikihito
authors.initials: M
authors.lastname: Hayashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Sachiko
authors.initials: S
authors.lastname: Takenoshita-Nakaya
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takeba
authors.forename: Minoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takagi
authors.forename: Masami
authors.initials: M
authors.lastname: Tanaka
authors.forename: Takehito
authors.initials: T
authors.lastname: Otsubo
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kobayashi
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D044466:Asian People; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D006801:Humans; D006900:Hydroxylation; D007413:Intestinal Mucosa / Q000201:enzymology*; D007421:Intestine, Small / Q000201:enzymology*; D064747:Lansoprazole; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008875:Middle Aged; D016577:Pancreaticoduodenectomy; D021381:Protein Transport
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D064747:Lansoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19