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Novel opioid peptides derived from alphas1-casein and mucin stimulatory effect in the rat intestine

AuthorsFernández-Tomé, Samuel ; Martínez-Maqueda, D. ; Girón, Rocío; Goicoechea, Carlos; Tabernero, María; Largo, Carlota; Miralles, Beatriz ; Recio, Isidra
Issue Date2018
Citation2nd International Conference on Food Bioactives and Health (2018)
AbstractThe presence of opioid peptides encrypted within the sequence of milk proteins was already reported in 1979. The gastrointestinal tract express opioid receptors and orally administered food-derived opioid peptides have shown to influence postprandial metabolism, prolongation of gastrointestinal tract and to exert effects on the immune system, among others. In addition, it was found that the opioid peptide β-casomorphin-7 was able to induce intestinal mucin relea se in intestinal mucin-producing ce lis by interaction with μ-opioid receptors located in the cell surface. Our group had previously shown the mucin secretory activity in HT29-MTX cells of various αs1-casein fragments with favourable structure to bind opioid receptors. In this study the activity of five αsl-casein peptides containing the core structure YFY has been evaluated in guinea pig ileum. lt was found that peptides 144YFYPEL149 and 144YFYPE148 exerted opioid agonistic activity. Molecular docking with these sequences explained the lack of activity found for 144YFYP147 in comparison with 144YFYPEL149, dueto differences in flexibility at the third intracellular loop of the μ-opioid receptor and the interaction with Pro at the peptide C-terminus that forced residues Arg148 and Glu166 from the receptor to m ove towards the interior of the binding pocket. A casein hydrolysate containing these peptides was orally administered to Zucker rats for 8 weeks. lt was observed a significant increase in 0-linked glycoproteins in faeces after 2 and 8 weeks. In addition, the expression for genes that encoded the secreted MUC2 and the membrane-bound MUC3 was higher in ileum and colon in comparison with the control group. This study demonstrates the opioid agonistic activity of various αs1-casein fragments and the in vivo effect on mucus secretion of a casein hydrolysate containing these sequences.
DescriptionResumen del trabajo presentado a la 2nd International Conference on Food Bioactives and Health, celebrada en Lisboa (Portugal) del 26 al 28 de septiembre de 2018.
Appears in Collections:(CIAL) Comunicaciones congresos
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