Intestinal perfusion induces rapid activation of immediate-early genes in weaning rats

C-fos and c-jun are immediate-early genes (IEGs) that are rapidly expressed after a variety of stimuli. Products of these genes subsequently bind to D NA regulatory elements of target genes to modulate their transcription. In rat small intestine, IEG mRNA expression increases dramatically after refee ding following a 48-h fast. We used an in vivo intestinal perfusion model t o test the hypothesis that metabolism of absorbed nutrients stimulates the expression of IEGs. Compared with those of unperfused intestines, IEG mRNA levels increased up to 11 times after intestinal perfusion for 0.3-4 h with Ringer solutions containing high (100 mM) fructose (HF), glucose (HG), or mannitol (HM). Abundance of mRNA returned to preperfusion levels after 8 h. Levels of c-fos and c-jun mRNA and proteins were modest and evenly distrib uted among enterocytes lining the villi of unperfused intestines. HF and HM perfusion markedly enhanced IEG mRNA expression along the entire villus ax is. The perfusion-induced increase in IEG expression was inhibited by actin omycin-D. Luminal perfusion induces transient but dramatic increases in c-f os and c-jun expression in villus enterocytes. Induction does not require m etabolizable or absorbable nutrients but may involve de novo gene transcrip tion in cells along the villus.