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.
- SourceAvailable from: Joakim Strandberg
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- "Antisecretory factor (AF) is an endogenous 43 kDa protein that is expressed in all mammalian tissues and plasma investigated so far (Johansson et al., 1995, 2009; Lange et al., 1999; Lange and Lönnroth, 2001; Ulgheri et al., 2010). The protein was named AF due to its capacity to counteract enterotoxin-induced intestinal hypersecretion, but later studies have shown that AF is also a potent anti-inflammatory agent (Johansson et al., 1997a, 2013; Eriksson et al., 2003; Davidson and Hickey, 2004a,b; Graber et al., 2011; Mane et al., 2011). "
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. DOI:10.3389/fncel.2014.00013 · 4.18 Impact Factor
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- "In the present study we failed to identify an activation enzyme for AF in the liver. AF is expressed in the small intestine  and it is possible that the activation of AF occurs locally in the intestinal wall. In the study of Helsby and coworkers  it was found that a number of enzymes in the intestine changed their expression after intake of defined cereals. "
ABSTRACT: Antisecretory factor (AF) inhibits pathologic fluid secretion and inflammation. AF is expressed in most tissues and is secreted into the blood. Challenge with bacterial enterotoxins increases AF activity. The plasma level of active AF is also increased after intake of certain food constituents, such as specially processed cereals, SPC. The exact molecular events that mediate these responses have remained obscure. The objective of this study was to investigate changes in protein expression in liver after SPC diet. Rats were fed SPC or standard rodent diet for 18 d. The induction of AF in plasma was tested by ELISA. Changes in the liver proteome were analyzed by using 2D DIGE and LC-MS/MS. Further characterizations were done with Western blot and immunohistochemistry studies. The AF activity was increased after intake of SPC. Equivalent to recombinant AF, 6.6 ± 1.09 ng/well could be detected in control plasma compared to 26 ± 5.73 ng/well in plasma after SPC treatment. We found that the protein level of glutathione S-transferase mu (GST mu) was significantly up-regulated 1.2-fold in rat liver after stimulation with SPC (wheat). The result was further confirmed by Western blot analysis. Immunohistochemistry showed staining for GST mu1 and AF preferentially in the central parts of the liver lobuli. Given the known role of GST mu1 in inducing defense, our results suggest that SPC-induced GST mu1 up-regulation can contribute to the positive clinical effects seen by SPC treatment.Nutrition 12/2010; 27(9):949-54. DOI:10.1016/j.nut.2010.09.009 · 3.05 Impact Factor
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- "At least part of the activity of the diet can be reproduced by a feed containing certain sugars and amino acids (Lange and Lonnroth, 2001). Both sugars and amino acids stimulate the production of a partly purified protein, referred to as antisecretory factor, which regulates fluid balance (Lange and Lonnroth, 2001). A cloned peptide was shown to be an active region of this protein ( Johansson et al., 1997, 1995). "
ABSTRACT: There is increasing evidence that even low levels of blast cause brain injury, but little is known about their thresholds and mechanisms. Exposure of rats to 10-60 kPa blasts elevate intracranial pressure (ICP) in a dose-dependent manner and impair cognitive function. We have evaluated a prophylactic measure against these brain injuries in a rat animal model, consisting of feeding them processed cereal. This type of feed is known to ameliorate disturbances in secretion of body fluids and to have anti-inflammatory effects. In humans, intake of processed cereals is effective against intestinal diarrhea and also reduces the symptoms of Ménière's disease. Rats were given either standard laboratory feed or processed cereal feed for 2 weeks before exposure to blast in a shock tube. The ICP was monitored at different time points up to 1 week after exposure to a 60-kPa blast, and for up to 24 h after exposure to a 30-kPa blast. Maximal ICP elevation was reached at 10 h in both groups. In the group of rats on standard feed exposed to 60 kPa, an ICP increase of 145% was noted at 10 h, and the corresponding increase in the rats fed processed cereal feed was only 50%. In rats exposed to a 30-kPa blast, those fed standard feed and processed cereal feed demonstrated increases of ICP of 80% and 40%, respectively. Cognitive function as measured by the Morris water maze was assessed in other groups of rats at 2 days after exposure to 10- or 30-kPa blasts. Their performance was significantly impaired at both exposure levels in rats on standard feed, but no functional impairment was seen in rats fed processed cereal feed.Journal of neurotrauma 10/2009; 27(2):383-9. DOI:10.1089/neu.2009.1053 · 3.97 Impact Factor