Inhibitory effect of experimental colitis on fluid absorption in rat jejunum: role of the enteric nervous system, VIP, and nitric oxide

Abstract

Impairment of small intestinal absorption has been described in patients with ulcerative colitis and in animal models of experimental colitis. The pathophysiology of this dysfunction has not been elucidated. The aim of this study was to investigate the effect of chemical colitis on jejunal fluid absorption and determine the role of the enteric nervous system and some putative neurotransmitters. In a rat model of iodoacetamide-induced colitis, jejunal net fluid absorption was evaluated by the in vivo single-pass perfusion technique. The effects of 1) tetrodotoxin (TTX), 2) benzylalkonium chloride (BAC), 3) capsaicin, 4) vasoactive intestinal polypeptide (VIP) antagonism, 5) nitric oxide (NO) synthase (NOS) inhibition, and 6) 5-hydroxytryptamine type 3 and 4 (5-HT3 and 5-HT4) receptor antagonism on the changes in fluid movement were investigated. A significant decrease in jejunal net fluid absorption was found 2 and 4 days after colitis induction: 26 (SD 14) and 28 (SD 19) μl·min−1·g dry intestinal wt−1, respectively [ P < 0.0002 compared with sham rats at 61 (SD 6.5) μl·min−1·g dry intestinal wt−1]. No histological changes were evident in jejunal sections. TTX and BAC reversed this decrease in fluid absorption: 54 (SD 13) and 44 (SD 14) μl·min−1·g dry intestinal wt−1 ( P = 0.0005 and P = 0.019, respectively, compared with colitis). Ablation of capsaicin-sensitive primary afferent fibers had a partial effect: 45 (SD 5) μl·min−1·g dry intestinal wt−1 ( P = 0.001 and P = 0.003 compared with colitis and sham, respectively). Constitutive and neuronal NOS inhibition and VIP antagonism returned jejunal net fluid absorption to normal values: 66 (SD 19), 61 (SD 5), and 56 (SD 14) μl·min−1·g dry intestinal wt−1, respectively. 5-HT3 and 5-HT4 receptor antagonism had no effect. Chemical colitis is associated with a significant decrease in jejunal net fluid absorption. This decrease is neurally mediated and involves VIP- and NO-related mechanisms.

The Role of Transient Receptor Potential Vanilloid 1 (Trpv1) Receptors in Dextran Sulfate-Induced Colitis in Mice

“…Neurotensin stimulated intestinal wound healing after chronic inflammation (Brun et al 2005). Antagonism of vasoactive intestinal polypeptide returned jejunal fluid absorption to normal values in iodoacetamide-evoked colitis in rats (Mourad et al 2006). Chronic administration of galanin attenuated TNBS-induced colitis in rats (Talero et al 2007).…”

Localized colonic inflammation increases cytokine levels in distant small intestinal segments in the rat

“…These include delay in gastric emptying, altered motility, reduced absorption of nutrients, water and electrolytes, as well changes in enteric nervous system structure and/or function (Andersson et al, 1971;Arvanitakis, 1979;Barada et al, 2001;Binder and Ptak, 1970;Chakravarti et al, 1973;Jacobson et al, 1995;Mourad et al, 2006;Rao et al, 1987;Safieh-Garabedian et al, 1997;Salem and Truelove, 1965;Zetzel et al, 1942). Since these abnormalities take place with or without overt signs of inflammation, the up regulation of pro-inflammatory cytokines might serve as a molecular substrate for the extra colonic changes reported in clinical and experimental colitis.…”

“…Furthermore, decreased expression of small intestinal disaccharidases was reported in ulcerative colitis (Arvanitakis, 1979). We have demonstrated before that induction of inflammation in the colon of experimental animals was associated with decreased jejunal absorption of alanine, glucose, and fluid without evident signs of inflammation (Barada et al, 2001;Mourad et al, 2006). The exact causes of this small bowel dysfunction are not known.…”

“…While CD can affect any segment of the GI tract, UC is thought to be restricted to the colon. Colitis in humans and experimental animals, however, may be associated with small bowel dysfunction, including altered motility and malabsorption of fat, carbohydrates, proteins, minerals, vitamins, water and D-xylose (Andersson et al, 1971; Barada et al, 2001;Binder and Ptak, 1970;Chakravarti et al, 1973;Mourad et al, 2006;Salem and Truelove, 1965;Zetzel et al, 1942). Furthermore, decreased expression of small intestinal disaccharidases was reported in ulcerative colitis (Arvanitakis, 1979).…”

Enhanced excitability of guinea pig inferior mesenteric ganglion neurons during and following recovery from chemical colitis

“…In addition to neuromuscular plasticity within the region of inflammation, there are often changes in neuromuscular function outside this area. These include reduced small bowel motility or intestinal secretory dysfunction during localized colitis in humans (2,9,35,37,48,58) and in experimental models (3,4,10,23,24,44). Systemic inflammatory cytokines or other endocrine signals may directly stimulate the upper bowel (4), but it is equally likely that there is a neural mechanism for altered upper gut dysfunction.…”