RT Journal Article SR Electronic T1 Characterization of rat small intestinal cytochrome P450 composition and inducibility. JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 322 OP 328 VO 24 IS 3 A1 Q Y Zhang A1 J Wikoff A1 D Dunbar A1 L Kaminsky YR 1996 UL http://dmd.aspetjournals.org/content/24/3/322.abstract AB The composition and inducibility of cytochrome P450 (P450) in rat small intestinal epithelial cells were investigated with the use of RNA-polymerase chain reaction and immunoblot techniques. The complement of intestinal P450s is more restricted than hepatic forms. P450s 1A1, 2B1, and 3A1 were detected in enterocytes of untreated rats and were inducible by beta-naphthoflavone (BNF), phenobarbital, and pregnenolone-16alpha-carbonitrile or dexamethasone, respectively. In addition, P450s 2C6 and 2C11 were both constitutively expressed at low levels. In contrast, several P450 forms, which are found in the liver, were not detected in enterocytes of untreated or induced rats, including P450s 2A1, 2B2, 2E1, 3A2, and 4A1. P4501A2 mRNA was detected only in BNF-induced rat small intestine and at levels that did not result in its detectable translation. The most prominent inducible form in rat small intestine is P4501A1. Its inducibility diminishes markedly along the length of the small intestine from the duodenum to the ileum. Furthermore, the induction of P4501A1 in enterocytes was affected by the route of administration of the inducing agent. Thus, intestinal P4501A1 was more sensitive to orally administered BNF, whereas induction of hepatic P4501A1 was more sensitive to intraperitoneal administered BNF. Overall, the results demonstrate the differential regulation of P450s between the liver and small intestine, and provide a basis for further studies in assessing the potential of intestinal P450s to protect against orally ingested polycyclic aromatic hydrocarbon carcinogens.