Role of 5-hydroxytryptamine type 3 receptors in rat intestinal fluid and electrolyte secretion induced by cholera and Escherichia coli enterotoxins.

Mourad, Fadi H.; O'donnell, L. J. D.; Dias, Jorge Amil; Eo, Ogutu; André, Eunice; Turvill, James; Farthing, M. J. G.

doi:10.1136/gut.37.3.340

Cited by 60 publications

(50 citation statements)

References 31 publications

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“…Studies with fish tetrodotoxin (TTX) showed that CT interacts with the enteric nervous system, inducing the secretion of neurohormones such as 5-hydroxytryptamine and vasoactive intestinal peptide (61,62) . LT is the major virulence factor of enterotoxigenic E. coli; it was found that LT binds to several brush-border galactoproteins only weakly recognised by CT, and it was suggested that binding of LT to this additional receptors might have a role in intestinal secretion pathophysiology (59,63) . Recent studies demonstrated that, beyond its ability to bind to different glycolipids on the surface of enterocytes, LT binds to LPS on the surface of E. coli (64) .…”

Section: Antisecretory Factor and Gut Healthmentioning

confidence: 99%

Antisecretory factor as a potential health-promoting molecule in man and animals

2010

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Antisecretory factor (AF) is a protein secreted in plasma and other tissue fluids in mammals with proven antisecretory and anti-inflammatory activity; its immunohistological distribution suggests a role in the immune system. The expression level and the distribution of AF protein are altered during an immunological response. Exposure to bacterial toxins induces secretion of AF in plasma, probably reflecting a natural defence mechanism to agents causing diarrhoea, thereby contributing to a favourable clinical outcome and disease termination. An increase of AF levels in plasma by dietary means, such as specially processed cereals (SPC), has been demonstrated in human subjects and animals. Administration of SPC to patients affected by inflammatory bowel disease, gastroenteritis and Ménière's disease relieved symptoms and improved quality of life. A recent study showed the positive effect of SPC diet supplementation on prevention of the effects of exposure to low levels of blast overpressure in rats, reducing the extent of intracranial pressure increase and cognitive function impairment. AF-rich egg yolk powder improved health status in children suffering acute and chronic diarrhoea, reducing the frequency and increasing the consistency of stools. This kind of functional food could be used for prophylaxis in populations exposed to a high risk of morbidity and mortality caused by diarrhoea and as a complementary therapy in patients affected by chronic intestinal inflammatory disease to improve well-being. In pig husbandry AF-inducing diets, owing to their antisecretory activity and anti-inflammatory action, are a suitable option as an alternative to antibiotic growth promoters to counteract post-weaning diarrhoea.

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Section: Antisecretory Factor and Gut Healthmentioning

confidence: 99%

Antisecretory factor as a potential health-promoting molecule in man and animals

2010

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“…Therefore, several efforts have been made to search for promising drugs that could be used to treat cholera more efficiently. These methods include inhibitors of cholera toxin receptor binding (Pickens et al, 2004), 5-hydroxytryptamine receptor antagonists (Mourad et al, 1995;Turvill and Farthing, 1997), somatostatin receptor agonists (Farthing, 1996), enkephalinase inhibitors (Cézard et al, 2001), and CFTR inhibitors (Muanprasat et al, 2004(Muanprasat et al, , 2007. Several natural products isolated from plants have also been used as sources of pharmaceuticals and as ingredients of traditional medicines (Phillipson, 1994).…”

mentioning

confidence: 99%

A Natural Plant-Derived Dihydroisosteviol Prevents Cholera Toxin-Induced Intestinal Fluid Secretion

Pariwat

Homvisasevongsa²,

Muanprasat³

et al. 2007

J Pharmacol Exp Ther

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Stevioside and its major metabolite, steviol, have been reported to affect ion transport in many types of tissues, such as the kidney, pancreas, and intestine. The effect of stevioside, steviol, and its analogs on intestinal Cl Ϫ secretion was investigated in a human T84 epithelial cell line. Short-circuit current measurements showed that steviol and analogs isosteviol, dihydroisosteviol, and isosteviol 16-oxime inhibited in a dosedependent manner forskolin-induced Cl Ϫ secretion with IC 50 values of 101, 100, 9.6, and 50 M, respectively, whereas the parent compound stevioside had no effect. Apical Cl Ϫ current measurement indicated that dihydroisosteviol targeted the cystic fibrosis transmembrane regulator (CFTR). The inhibitory action of dihydroisosteviol was reversible and was not associated with changes in the intracellular cAMP level. In addition, dihydroisosteviol did not affect calcium-activated chloride secretion and T84 cell viability. In vivo studies using a mouse closed-loop model of cholera toxin-induced intestinal fluid secretion showed that intraluminal injection of 50 M dihydroisosteviol reduced intestinal fluid secretion by 88.2% without altering fluid absorption. These results indicate that dihydroisosteviol and similar compounds could be a new class of CFTR inhibitors that may be useful for further development as antidiarrheal agents.

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“…The dose of these antagonists is capable of inhibiting cholera toxininduced secretion (7,38,39). Values are means (SD) and 95% confidence intervals (CI) in each group of animals.…”

Section: No Synthase Inhibition Vip Antagonism and 5-ht 3 And 5-ht4mentioning

confidence: 99%

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

Mourad¹,

Barada²,

Rached³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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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.

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Role of 5-hydroxytryptamine type 3 receptors in rat intestinal fluid and electrolyte secretion induced by cholera and Escherichia coli enterotoxins.

Cited by 60 publications

References 31 publications

Antisecretory factor as a potential health-promoting molecule in man and animals

Antisecretory factor as a potential health-promoting molecule in man and animals

A Natural Plant-Derived Dihydroisosteviol Prevents Cholera Toxin-Induced Intestinal Fluid Secretion

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

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