Several studies have suggested that gastrointestinal peptides can produce trophic changes in the small intestine epithelium. In a previous study utilizing a rat fetal intestine transplant model, we reported that chronic, continuous, systemic administration of gastrin-17 increased carbohydrate absorption 2.5-fold and protein absorption 1.3-fold. The present study was designed to evaluate the effect of chronic luminal perfusion of gastrin on substrate absorption in rat mature small intestine. A 10-cm segment of mid small intestine was isolated with both ends brought out as abdominal wall stomas (creating a Thiry-Vella loop) and bowel continuity was established by end-to-end anastomosis. After a 1-week recovery, the tips of two catheters were positioned at approximately 3 and 6 cm from the proximal end of the isolated small intestine segment. A 14-day continuous luminal perfusion was accomplished by connecting the other ends of the catheters to subcutaneously placed osmotic pumps filled to deliver saline (control; N = 10) or gastrin-17 (13.5 nM/kg/day; N = 7). At the completion of the luminal perfusion, intestinal absorption was determined with labeled substrates [14C]galactose and [14C]glycine) using a closed, recirculation technique. Absorption (microM/cm2 small intestine) of galactose in the control animals was 1.44 +/- 0.18 and for the gastrin infused rats, it was 6.56 +/- 0.46. Glycine absorption was 1.63 +/- 0.31 for the control group and 7.83 +/- 0.62 for the gastrin infused group. Thus, in this rat model, intraluminal gastrin infusion was capable of increasing carbohydrate (galactose) absorption 456% (P less than 0.01) and protein (glycine) absorption 480% (P less than 0.01). These data represent the first demonstration that intraluminal gastrin can influence small intestine mucosal function by enhancing substrate absorption.(ABSTRACT TRUNCATED AT 250 WORDS)