RT Journal Article
SR Electronic
T1 EXPRESSION PROFILES OF DRUG-METABOLIZING ENZYME CYP3A AND DRUG EFFLUX TRANSPORTER MULTIDRUG RESISTANCE 1 SUBFAMILY mRNAS IN RAT SMALL INTESTINE
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1235
OP 1239
DO 10.1124/dmd.31.10.1235
VO 31
IS 10
A1 Kohji Takara
A1 Noriaki Ohnishi
A1 Sayo Horibe
A1 Teruyoshi Yokoyama
YR 2003
UL http://dmd.aspetjournals.org/content/31/10/1235.abstract
AB The purpose of this study is to examine the expression profiles of CYP3A1, CYP3A2, CYP3A9, and CYP3A18 mRNAs as well as multidrug resistance (mdr)1a and mdr1b mRNAs in the liver and small intestine of normal male Wistar rats using a reverse transcription-polymerase chain reaction (PCR). In the rat liver, the PCR products for CYP3A1, CYP3A2, and CYP3A18 were readily detectable, whereas CYP3A9 was slightly and mdr1a and mdr1b barely detected. Surprisingly, no PCR products for CYP3A1 and CYP3A2 were detected in the small intestine, but those for CYP3A9, CYP3A18, and mdr1a were readily detectable, and a faint band for mdr1b was also observed. Both CYP3A9 and CYP3A18 levels were found to be high in the duodenum and decreased from the top to bottom of the gut, indicating regional differences in both CYP3A9 and CYP3A18 expression in the small intestine. In contrast, mdr1a expression increased gradually from the upper to lower intestine. Consequently, it was suggested that drug metabolism in the small intestine of normal rats was mediated by CYP3A9 and CYP3A18 rather than CYP3A1 and CYP3A2. Also, regional differences of CYP3A9, CYP3A18, and mdr1a expression were found in the small intestine. The distributions of CYP3A9 and CYP3A18 were different from the distribution of mdr1a, suggesting the cooperative action of drug clearance pathways. This information is important to drug metabolism research based on ex vivo and in vivo studies using rats. The American Society for Pharmacology and Experimental Therapeutics