DIFFERENCES BETWEEN NUCLEAR RUN-OFF AND MESSENGER-RNA LEVELS FOR MULTIDRUG-RESISTANCE GENE-EXPRESSION IN THE CEPHALOCAUDAL AXIS OF THE MOUSE INTESTINE

P-glycoprotein is a multidrug transporter encoded by the mdr3 gene in the mouse intestinal epithelium. The aims of this study were to charac terize the mdr3 gene expression in the cephalocaudal axis of the intes tine in adult animals and during perinatal development, and to define the molecular mechanism responsible for the heterogeneous expression o f the gene along the cephalocaudal axis. RNA extracted from stomach, d uodenum, jejunum, ileum, cecum and colon was hybridized by slot blot a nd Northern blot using a mdr3 cDNA probe. The regulation of gene expre ssion was investigated examining the rate of transcription by nuclear run-off analysis. Transport studies of rhodamine 123, a substrate of P -glycoprotein, were performed in everted jejunum and ileum. The level of mdr3 mRNA and P-glycoprotein found in ileum was 6-fold higher than the level found in duodenum. The regional pattern of mdr3 gene express ion is established in the intestine of 10-day-old animals. Similar mdr 3 hybridization signal in nuclear run-off assay was found in nuclei of enterocytes isolated from jejunum and ileum, suggesting that the hete rogeneous expression of the mdr3 gene in the cephalocaudal axis of the small bowel may be predominantly regulated at the post-transcriptiona l level. Transport rate of rhodamine 123 from the serosal to mucosal s ide in everted ileum was higher than the rate of transport found in je junum. These results indicate that enterocytes of the ileum may be mor e actively involved in the P-glycoprotein-mediated transport of xenobi otics into the intestinal lumen.