Neuronal involvement in the effect of an antisecretory factor-derived peptide on induced secretion in the porcine small intestine

Abstract

The antisecretory factor is a protein inhibiting enterotoxin-induced intestinal inflammation and hypersecretion. We studied the signaling pathway of three antisecretory factor-derived peptides (A1, A3 and A4) in the proximal and distal porcine small intestine. In vivo (ligated loops), only A3 significantly reduced the cholera toxin-induced fluid accumulation and only in proximal loops. A3 and A4 reduced Escherichia coli heat-labile enterotoxin-induced fluid accumulation in the proximal segment, whereas A1 and A3 reduced the Escherichia coli heat-labile enterotoxin-induced fluid accumulation in the distal segment. The secretory response to intraluminally added 5-hydroxytryptamine was not significantly inhibited by the peptides. The amount of intraluminal 5-hydroxytryptamine accumulated in cholera toxin-stimulated loops from the proximal segment was significantly reduced by A3. In vitro,the effect of A3 on secretagogue-induced increases in short-circuit current was recorded from proximal small intestine by the Ussing chamber technique. A3 decreased the tetrodotoxin sensitive effect of substance P. The in vivo results suggest that the antisecretory effect may involve inhibition of the local release of 5-hydroxytryptamine induced by cholera toxin, but not inhibition of secretory reflexes induced by 5-hydroxytryptamine. The in vitro results suggest that the effect of A3 lies beyond the surface epithelium, and involves mucosal neuronal structures.

Antisecretory Factor Peptide AF-16 Inhibits the Secreted Autotransporter Toxin-Stimulated Transcellular and Paracellular Passages of Fluid in Cultured Human Enterocyte-Like Cells

“…A region of AF that supports its antisecretory activity has been identified between residues 36 and 51, located in the N-terminal part of the full-length protein (14,(17)(18)(19)(20). Experimentally, AF inhibits the intestinal secretion of fluids induced by a variety of toxins, including CT (6,7,14,17,(21)(22)(23)(24)(25)(26), Campylobacter toxin (24,27), Escherichia coli heat-labile enterotoxin (LT) (18,23) and heatstable enterotoxins (ST) (23,25,28), CDT (14,15,21), and Dinophysis toxin (24). Moreover, AF and the AF peptide containing the active peptide sequence from residues 36 to 51 have been shown to block the out-in permeation of 36 Cl in nerve cell membranes isolated from rabbit Dieter cells (20,29,30).…”