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

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-HT(3) and 5-HT(4)) 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) microl x min(-1) x g dry intestinal wt(-1), respectively [P < 0.0002 compared with sham rats at 61 (SD 6.5) microl x min(-1) x 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) microl x min(-1) x 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) microl x min(-1) x 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) microl x min(-1) x g dry intestinal wt(-1), respectively. 5-HT(3) and 5-HT(4) 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.

Effect of theophylline on L-alanine absorption in the rat jejunum.

The effect of theophylline on the accumulation of L-alanine (Ala) by the rat jejunum and the mechanism involved has been investigated. Ala is rapidly accumulated by the jejunal strips in vitro and saturation is reached between 10 and 15 min. An In/Out ratio of 2.55 reflects the presence of an active component in the overall transport mechanism. Ala accumulation shows a tendency toward saturation as cellular Ala concentration increases. In the absence of Na+, Ala accumulation is reduced and a direct relationship is observed between alanine concentration in the incubation medium and its intracellular concentration. Alanine accumulation is inhibited when theophylline (TH) concentration in the incubation medium is greater than 0.5 mM. A maximum inhibition of approximately 50% in the presence of 10 mM theophylline is observed. Further inhibition (57-65%) is observed when the jejunal strips are incubated in a Na+-free medium containing 10 mM theophylline. Single-pass perfusion of the rat jejunum shows that the presence of 0.5 mM TH in the perfusate, simulating therapeutic doses, did not affect Ala absorption. However, about 55% inhibition of Ala absorption was observed when 10 mM TH was included in the perfusate. In conclusion, it could be stated that in both in vitro and in vivo studies high toxic but not therapeutic doses of TH inhibit intestinal Ala uptake. The mechanism of inhibition may be attributed to a non-carrier mediated mechanism with a minor effect noticed on Ala carrier system.