Effects of antisecretory factor-derived peptides on contractions in guinea pig colon

Faculty of Veterinary Science, The University of Zimbabwe, Harare, Zimbabwe
Comparative Biochemistry and Physiology - Part A Molecular & Integrative Physiology (Impact Factor: 1.97). 11/2004; 139(2):143-148. DOI: 10.1016/j.cbpb.2004.08.001


Two antisecretory factor (AF)-derived peptides have been studied in relation to effects on motility of guinea pig colon. Colon segments were isolated from adult guinea pigs and incubated in Tyrode Ringer. Motility was measured as the force and frequency of contractions upon addition of the derived peptides AF 1 (8 amino acids (aa)) and AF 3 (10 amino acids). At the lowest concentration (5 pM), peptide AF 1 induced a negative effect on the force of contraction in colon segments; an effect that was abolished by the cholinergic agonist carbachol. Peptide AF 3 induced a significant increase in the force of colon contractions at all concentrations (5–180 pM), with carbachol only reducing the effect of peptide AF 3 at a concentration of 15 pM. Both peptides increased contractile frequency, although the overall response was lower for peptide AF 3 than for peptide AF 1. It is concluded that antisecretory factor-derived peptides may play a role in regulating colon motility such that under pathophysiological conditions, they may serve to hasten the evacuation of noxious agents from the large intestine.

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    ABSTRACT: Antisecretory Factor (AF) is a protein that has been implicated in the suppression of intestinal hypersecretion and inflammation. Intestinal secretion and inflammation are partly under local and central neural control raising the possibility that AF might exert its action by modulating neural signaling. In the present study we have investigated whether AF can modulate central synaptic transmission. Evoked glutamatergic and GABAergic synaptic transmissions were investigated using extracellular recordings in the CA1 region of hippocampal slices from adult rats. AF (0.5 microg/ml) suppressed GABA(A)-mediated synaptic transmission by about 40% while having no effect on glutamatergic transmission. Per oral administration of cholera toxin as well as feeding of rats with a diet containing hydrothermally processed cereals, known to upregulate endogenous AF plasma activity, mimicked the effect of exogenously administered AF on hippocampal GABAergic transmission. Our results identify AF as a neuromodulator and further raise the possibility that the hippocampus and AF are involved in a gut-brain loop controlling intestinal secretion and inflammation.
    No preview · Article · Aug 2005 · Regulatory Peptides
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    ABSTRACT: 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.
    Preview · Article · Dec 2010 · Nutrition Research Reviews
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    ABSTRACT: The endogenous antisecretory factor (AF) protein and peptide AF-16, which has a sequence that matches that of the active terminal N-region of AF, both inhibit the increase in the epithelial transport of fluid and electrolytes induced by bacterial toxins in animal and ex-vivo models. We conducted a study to investigate the inhibitory effect of peptide AF-16 against the increase of transcellular passage and paracellular permeability promoted by the secreted autotransporter toxin (Sat), which belongs to the subfamily of serine protease autotransporters of Enterobacteriaceae (SPATEs) in a cultured cellular model of human intestinal epithelial barrier. Peptide AF-16 produced a concentration-dependent inhibition of the Sat toxin-induced increase in the formation of fluid domes, in the mucosal-to-serosal passage of D-[1-(14)C]-mannitol, and in the rearrangements in the distribution and protein expression of the TJs-associated ZO-1 and occludin in cultured human enterocyte-like Caco-2/TC7 cell monolayers. In addition, we show that peptide AF-16 also inhibits the cholera toxin-induced increase of transcellular passage, and the Clostridium difficile toxins-induced effects on paracellular permeability and TJs proteins organization in Caco-2/TC7 cell monolayers. Treatment of cell monolayers by the lipid rafts disorganizer, methyl-β-cyclodextrin abolishes the inhibitory activity of peptide AF-16 at transcellular passage level and not modify the peptide effect at paracellular level. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
    Preview · Article · Dec 2014 · Infection and Immunity