The antisecretory factor: Synthesis, anatomical and cellular distribution, and biological action in experimental and clinical studies
ABSTRACT The antisecretory factor (AF) is a 41-kDa protein that provides protection against diarrheal diseases and intestinal inflammation. Its cDNA has been cloned and sequenced. AF is highly potent, with 10–12 mol of recombinant AF being sufficient to counteract experimentally induced diarrhea in rat. The antisecretory activity is exerted by a peptide located between positions 35 and 50 of the AF sequence. Synthetic peptides based on this sequence are promising candidates for drugs to counteract intestinal hypersecretion, as well as imbalances of fluid transport in other body compartments. AF probably exerts its effects via nerves; AF immediately and potently inhibits ion transport across isolated nerve membranes from Deiters' cells. Immunocytochemistry has shown that AF is present in most tissues in the body, and in situ nucleic acid hybridization has shown that cells that store AF are also capable of AF synthesis. The endogenous plasma level of AF is increased by enterotoxins and by certain food constituents such as hydrothermally processed cereals. These cereals significantly improve clinical performance in patients suffering from inflammatory bowel diseases. AF-enhancing food also protects domestic animals against diarrheal diseases, and such feed has been used successfully in Swedish swine farming for the past 10 years. Increased understanding of AF action might result in expanded clinical applications and confirm that AF is an important regulator of homeostasis.
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ABSTRACT: Intake of specially processed cereal (SPC) stimulates endogenous antisecretory factor (AF) activity, and SPC intake has proven to be beneficial for a number of clinical conditions. The aim of the present study was to investigate the dosage relationship between SPC intake and plasma AF activity and to further correlate achieved AF levels to a biological effect. SPC was fed to rats in concentrations of 5, 10 or 15 % for 2 weeks. A further group was fed 5 % SPC for 4 weeks. AF activity and the complement factors C3c and factor H were analysed in plasma after the feeding period. Groups of rats fed the various SPC concentrations were subjected to a standardised freezing brain injury, known to induce increases in intracranial pressure (ICP). The AF activity in plasma increased after intake of SPC, in a dosage- and time-dependent manner. The complement factors C3c and factor H increased in a time-dependent manner. Measurements of ICP in animals fed with SPC prior to the brain injury showed that the ICP was significantly lower, compared with that of injured rats fed with a standard feed, and that the change was dose and time dependent. AF activity increases, in a dosage- and time-dependent manner, after intake of SPC. The inverse relationship between ICP after a head injury and the percentage of SPC in the feed indicate that the protective effect is, to a large extent, due to AF.The British journal of nutrition 11/2012; · 3.45 Impact Factor
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ABSTRACT: Tonic GABAergic inhibition regulates neuronal excitability and has been implicated to be involved in both neurological and psychiatric diseases. We have previously shown that the endogenous peptide antisecretory factor (AF) decreases phasic GABAergic inhibition onto pyramidal CA1 neurons. In the present study, using whole-cell patch-clamp recordings, we investigated the mechanisms behind this disinhibition of CA1 pyramidal neurons by AF. We found that application of AF to acute rat hippocampal slices resulted in a reduction of the frequency, but not of the amplitude, of spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 pyramidal neurons. Miniature inhibitory postsynaptic currents (mIPSCs), recorded in the presence of tetrodotoxin (TTX), were however not affected by AF, neither in CA1 pyramidal cells, nor in stratum radiatum interneurons. Instead, AF caused an increase of the tonic GABAA current in stratum radiatum interneurons, leaving the tonic GABAergic transmission in CA1 pyramidal cells unaffected. These results show that the endogenous peptide AF enhances tonic, but not phasic, GABAergic signaling in CA1 stratum radiatum interneurons, without affecting tonic GABAergic signaling in CA1 pyramidal neurons. We suggest that this increased tonic GABAergic signaling in GABAergic interneurons could be a mechanism for the AF-mediated disinhibition of pyramidal neurons.Frontiers in Cellular Neuroscience 01/2014; 8:13. · 4.47 Impact Factor
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ABSTRACT: We studied the response to high doses of egg yolk containing Antisecretory Factor (B221(®) , Salovum(®) ) in young children with acute diarrhoea, presenting to the Children's Hospital, Lahore, Pakistan. In a randomised, placebo controlled trial, 36 children aged 7 to 60 months with acute diarrhoea of unknown aetiology, with mild to moderate dehydration, were randomised to the Salovum(®) or placebo groups. Initially16 grams of Salovum(®) or ordinary egg yolk (placebo) mixed in oral rehydration salts was given, followed by 8 grams every 5 hours until recovery. The number and consistency of stools were recorded. The two groups were comparable in age, gender, duration of diarrhoea, hydration, and nutritional status, although the proportion with watery stools was higher in the Salovum(®) group (p = 0.04). Reduction in the frequency of stools was seen at 7 vs. 18 hours (p<0.0001) and normalising of stool consistency was 10 vs. 18 hours, p<0.03) in the Salovum(®) and placebo groups. The overall effect was 35 vs. 70 hours in the two groups (p = 0.001). No side effects were reported. High doses of AF in the form of Salovum(®) effectively and safely reduce childhood diarrhoea of a likely broad aetiology. This article is protected by copyright. All rights reserved.Acta Paediatrica 02/2014; · 1.97 Impact Factor