Administrative Information

المعلومات الادارية

عنوان المشروع- Project Title

بلغة اجنبية:

Neural Control of Water and Nutrient Absorption in the Small Intestine

باللغة العربية:

دور الجهاز العصبي في عملية امتصاص الماء و المواد المغذية عبر الأمعاء الدقيقة

الباحث الرئيسي Principal Investigator -

الاسم Name	المؤسسة Institution	الوظيفية Post	العنوان Address	العنوان الالكتروني e-mail	رقم الهاتف Telephone
Camille Nassar	Univ- Balamand	Prof.	Faculty of Medecin	camille.nassar@balamand.edu.lb	06-930279

الباحثون المشاركون Co-Workers

الاسم Name	المؤسسة Institution	العنوان الالكتروني e-mail
Nayef Saadé	AUB	nesaade@aub.edu.lb
Kassem Breydi	LAU	kb02@aub.edu.lb
Fadi Mourad	AUB	fmourad@aub.edu.lb

المدة التعاقدية للمشروع Duration -: ثلاث سنوات (3 years)

Scientific Information

المعلومات العلميّة

الهدف- Objectives

The goal of this study is to reveal the clinical implications of the ENS effects on nutrient absorption. We ask whether conditions characterized by altered neural activity in the intestine, such as neurogenic inflammation or diabetic neuropathies are associated with changes in nutrient absorption, and if so can the transport alterations be linked to the neural dysfunction.

ألانجازات المحققة Achievements -

In the first part, in vitro experiments were performed on Sprague-Dawley rats. The effects of different concentrations of xylocaine, tetrodotoxin (TTX), ketamine, and pentobarbital-Na+ on alanine uptake by isolated jejunal strips and mucosal scrapings were measured in normal rats and in rats subjected to chemical ablation of either their myenteric neurons and/or their afferents sensitive to capsaicin. All drugs tested reduced, in a dose dependent manner, alanine uptake by full thickness strips of normal rats.

Similar doses of the same chemicals were also needed to elicit significant changes in bezylalkonium chloride and neonatally treated rats with capsaicin. It is concluded that the enteric nervous system is involved in the regulation of jejunal alanine absorption, and this control is partially mediated by GABA-ergic and glutamatergic neurons..

Later, the effect of capsaicin on D-glucose absorption was studied in vivo using the single pass perfusion technique. Different concentrations of glucose ranging between 0.1 – 20 mM were perfused. The results show that capsaicin at 400 µM caused a significant inhibition of glucose absorption (45 – 50% , p<0.001) when glucose was perfused at 20 mM. Lower concentrations of glucose were not inhibited by equal concentrations of capsaicin. The effect of different concentrations of capsaicin (100 – 800 µM) on 0.1 to 20mM glucose uptake by jejunal strips was determined in vitro. The results demonstrate a significant decrease in glucose accumulation in the jejunal strips in a dose-dependent manner. The maximum effect (37.7% inhibition) was observed by 800µM at 20mM glucose.

Finally, a third set of in vivo experiments was performed to study the role of the ENS in the chemoreception process of amino acids in the lumen of the small intestine.Basal jejunal Ala absorption was significantly decreased for at least two hours with the instillation of 10 and 20mM Ala in the ileum. This inhibitory effect was totally abolished by TTX instilled in the ileum, subdiaphragmatic vagotomy and IV CGRP antagonist without affecting basal alanine absorption. Neonatal capsaicin treatment decreased basal Ala absorption but prevented any further drop with the instillation of Ala in the ileum. The presence of proline in the ileum significantly decreased basal jejunal absorption of both proline and Ala. The same inhibitory effect of jejunal Ala absorption was observed with the instillation of 20mM alanine in a distal jejunal segment. Similarly, basal Ala absorption from the ileum was significantly decreased by the presence of 20mM Ala in the jejunum

آفاق البحث Perspectives -

The above results demonstrate that the enteric neurons in the small intestine have a direct influence on the absorption of nutirents namely glucose and amino acids. Further studies are needed to establish whether impaired activity of the enteric neurons as a result of inflammation or neuropathies affect nutrient absorption.

المنشورات والمساهمات في المؤتمرات- Publications & Communications

1- Chemoreception of amino acids in the rat intestinal lumen regulates their own absorption: role of the enteric nervous system; Submitted for publication

2- Barada KA, Mourad FH, Sawah SI, Khoury C, Safieh-Garabedian B, Nassar CF, Saade NE. Localized colonic inflammation increases cytokine levels in distant small intestine segments in rats. Life Sci. 19; 79(21): 2032-42; 2006.

3- Mourad FH, Barada KA, Bou Rached NA, Khoury CI, Saade NE, Nassar CF. Inhibitory effect of experimental colitis on fluid absorption in rat jejunum: role of the enteric nervous system, VIP, and nitric oxide. Am J Physiol Gastrointest Liver Physiol.; 290(2): G262-8; 2006.

موجز باللغة العربية عن نتائج البحث Abstract in Arabic

غير متوفر N/A