Submitted on March 16, 2009
Revised on May 22, 2009
Accepted on June 15, 2009
Amino acids in the rat intestinal lumen regulate their own absorption from a distant intestinal site
Fadi H. Mourad1*, Kassem A Barada2, Carmen Khoury3, Tamim Hamdi3, Nayef E Saade4, and Camille F Nassar3
1 American University of Beirut Faculty of Medicine
2 American University of Beirut Medical Center
3 American University of Beirut
4 American Univ Beirut
* To whom correspondence should be addressed. E-mail: fmourad{at}aub.edu.lb.
Background & aims: Intestinal nutrient transport is altered in response to changes in dietary conditions and luminal substrate level. It is not clear, however, whether an amino acid in the intestinal lumen can acutely affect its own absorption from distant sites. Our aim is to study the effect of an amino acid present in rat small intestinal segment on its own absorption from a proximal or distal site and elucidate the underlying mechanisms. Methods: The effect of instillation of alanine (Ala) in either jejunum or ileum on its own absorption at ileal or jejunal level was examined in vivo. The modulation of this intestinal regulatory loop by the following interventions was studied: tetrodotoxin (TTX) added to Ala, subdiaphragmatic vagotomy, chemical ablation of capsaicin sensitive primary afferent (CSPA) fibers and IV administration of calcitonin gene related peptide (CGRP) antagonist. In addition, the kinetics of jejunal Ala absorption and the importance of Na+-dependent transport were studied in vitro after instilling Ala in the ileum. Results: Basal jejunal Ala absorption [0.198±0.018µmol cm-1 20min-1 (mean±SD)] was significantly decreased with the instillation of 20mM Ala in the ileum or in an adjacent distal jejunal segment (0.12±0.015; p<0.0001 and 0.138±0.014; p<0.002, respectively). Comparable inhibition was observed in the presence of proline in the ileum. Moreover, basal Ala absorption from the ileum [0.169±0.025] was significantly decreased by the presence of 20mM Ala in the jejunum [0.103±0.027; p<0.01]. The inhibitory effect on jejunal Ala absorption was abolished by TTX, subdiaphragmatic vagotomy, neonatal capsaicin treatment and CGRP antagonism. In vitro studies showed that Ala in the ileum affects Na+-mediated transport and increases Km without affecting Vmax. Conclusion: Intraluminal amino acids control their own absorption from a distant part of the intestine, by affecting the affinity of the Na+-mediated Ala transporter, through a neuronal mechanism that involves CSPA and CGRP.
