The studies presented in this proposal are designed to evaluate the role of neural and endocrine mediators in the control of small intestinal absorption and secretion. Unlike previous investigations on small bowel absorption, we plan to study the response of jejunal and ileal absorption and secretion independent of the content. The general hypothesis is that the neural and circulating hormone responses to feeding facilitate normal basal small bowel absorption independent of lumenal solutes. We hypothesize that surgical interruption of normal neural pathways, as seen following upper gastrointestinal surgical procedures in patients, interferes with these absorptive processes. The role of these extralumenal mechanisms in the control of post prandial absorption has not been previously studied. We propose to study the effects of feeding on isolated neuro- vascularly intact jejunal and ileal loops that have been surgically transplanted out of continuity with the rest of the gastrointestinal tract (Thiry Vella loops). These studies will be conducted in unanesthetized dogs. The experiments described have the following specific aims: 1. To determine the normal intestinal following feeding for water and electrolyte absorption/secretion in the neurovascularly intact isolated small bowel loop. The role of mixed meals, carbohydrate meals, and protein meals will be examined. 2. To identify the pathways that mediate the absorptive response be selective receptor blockade. 3. To determine the role of enteral feeding on small bowel absorption and secretion of water and electrolytes in isolated Thiry-Vella Loops. 4. To define the role of feeding on water and ion flux before and after vagotomy in Thiry-Vella Loops. 5. To identify the role neural innervation on post-prandial water and electrolyte transport by studying Thiry-Vella loops pre and post autotransplantation. This will eliminate all neural connections. This work should have direct application to a better understanding of several common gastrointestinal diseases including malabsorption syndrome, non-specific diarrhea irritable bowel syndrome, and postoperative small bowl function following gastrointestinal surgery.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Schools of Medicine
United States
Zip Code
Rongione, A J; Kusske, A M; Newton, T R et al. (2001) EGF and TGF stimulate proabsorption of glucose and electrolytes by Na+/glucose cotransporter in awake canine model. Dig Dis Sci 46:1740-7
Lane, J S; Whang, E E; Rigberg, D A et al. (1999) Paracellular glucose transport plays a minor role in the unanesthetized dog. Am J Physiol 276:G789-94
Whang, E E; Hines, O J; Reeve Jr, J R et al. (1997) Antisecretory mechanisms of peptide YY in rat distal colon. Dig Dis Sci 42:1121-7
Whang, E E; Dunn, J C; Mahanty, H et al. (1996) Endotoxin inhibitor prevents sepsis-induced alterations in intestinal ion transport. Am J Surg 172:341-4
Whang, E E; Dunn, J C; Liu, C D et al. (1996) Amiloride inhibits meal-stimulated colonic absorption. J Surg Res 60:303-6
Whang, E E; Dunn, J C; Joffe, H et al. (1996) Enterocyte functional adaptation following intestinal resection. J Surg Res 60:370-4
Bastidas, J A; Yeo, C J; Schmieg Jr, R E et al. (1990) The proabsorptive effect of D-ala2-metenkephalinamide is mediated by naloxone-sensitive opiate receptors in the isolated perfused ileum. Surgery 107:648-54
Bastidas, J A; Orandle, M S; Zinner, M J et al. (1990) Small-bowel origin of the signal for meal-induced jejunal absorption. Surgery 108:376-83
Yeo, C J; Bastidas, J A; Schmieg Jr, R E et al. (1989) Postreceptor mechanisms of small-bowel water and electrolyte transport. Surgery 106:408-14;discussion 414-5