UDP-glucuronosyltransferase UGT1A7 induced in rat small intestinal mucosa by oral administration of 2-naphthoflavone

In the rat intestine, UDP-glucuronosyltransferase (UGT) isoforms were highl y induced by oral administration of 2-naphthoflavone, as shown by intestina l UGT activity toward l-naphthol (1-NA). The greatest increase in UGT activ ity occurred in the duodenum. Using UGT1A6 cDNA as a probe, we obtained thr ee types of clones corresponding to UGT1A2, UGT1A6 and UGT1A7, in a ratio o f 1:1:8, from a cDNA library constructed from the 2-naphthoflavone-treated rat intestine. The induction of each isoform was evaluated by means of Nort hern blotting with isoform-specific probes. The mRNAs of UGT1A6 (glucuroniz ing various phenolic xenobiotics) and the mRNAs of UGT1A7 (glucuronizing th e ultimate carcinogenic metabolite of benzo(a)pyrene) were expressed consti tutively and were highly induced in the duodenum and proximal jejunum. S1 m apping showed that induction of the isoforms of the UGT1 family was more pr onounced in the liver than in the small intestine and that UGT1A7 was the m ajor UGT1 isoform in the small intestine of vehicle-treated rats and in tha t of 2-naphthoflavone-treated rats. These results indicate that, in rats, U GT1A7 is expressed constitutively and is particularly inducible in the smal l intestine. In the light of these results, we believe that the UGT1A7 isof orm would play an important role in glucuronidation in the small intestinal mucosa of rats.