Étude in vitro de la sensibilité de l'[alpha]-casozépine, décapeptide à activité benzodiazépine mimétique, à diverses protéases et peptidases du tractus gastro-intestinal. Étude comportementale chez le rat Wistar de l'activité anxiolytique des fragments F97 et F95 libérés par la pepsine

Abstract : [alpha]-Casozepine, a tryptic decapeptide from bovine [alpha]s1-casein, have in vitro an affinity for the benzodiazepine site of the central receptor GABAA (Lecouvey et al., 1997; Miclo et al., 2001). Some results display the anxiolytic potential of this peptide alone or within its hydrolysat, in vivo, in intra peritoneal administration and per os in Wistar rats (Guesdon et al., 2006; Miclo et al., 2001; Violle et al., 2007) and in human in oral administration (Kim et al., 2007; Messaoudi et al., 2005). To determine the sensitivity of [alpha]-casozepine in various proteolytic attacks, kinetics of gastric, pancreatic and intestinal hydrolyses, were realized in vitro with enzymes and following enzymatic systems; pepsin, trypsin, [alpha]-chymotrypsin, CorolasePPTm, brush border membranar vesicles rats enterocytes and enterocytes epithelium reconstituted by the Caco-2 cell line. For each of the conditions of studied hydrolysis, all the peptides fragments released were separated by liquid chromatography high-performance in inverted phase and characterized by mass spectrometry. These analyses underline the partial resistance of [alpha]-casozepine in some enzymes and enzymatic systems. [alpha]-Casozepine pepsic hydrolysis release in particular two peptide fragments: 91YLGYLEQ97 and 91YLGYL95, named F97 and F95 who turn out to be more resistant than [alpha]-casozepine in some used enzymes. So to allow a better understanding of the relation between structure of [alpha]-casozepine and the benzodiazepine mimetic function obtained in vivo, these peptides truncated in their carboxy-terminal party were tested in vivo with Wistar rat in intra peritoneal injection. They turn out to be also holders of anxiolytic activity. However no transfer of [alpha]-casozepine and fragments F97 and F95 was observed through the enterocyte epithelium reconstituted by the cellular model Caco-2 and this in spite of the various conditions of cultures and tested analyses
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Frédérique Balandras. Étude in vitro de la sensibilité de l'[alpha]-casozépine, décapeptide à activité benzodiazépine mimétique, à diverses protéases et peptidases du tractus gastro-intestinal. Étude comportementale chez le rat Wistar de l'activité anxiolytique des fragments F97 et F95 libérés par la pepsine. Autre. Institut National Polytechnique de Lorraine, 2008. Français. ⟨NNT : 2008INPL047N⟩. ⟨tel-01748691⟩

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