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-Casomorphin-7 Regulates the Secretion and the Expression of Gastrointestinal Mucins through a µ-Opioid Pathway
1 Inserm, U45; Lyon, IFR62; University Claude Bernard Lyon I, Faculte de Medecine R. Laennec, Lyon, F-69327, France
2 Department of Neuropharmacology, Cajal Institute, Consejo Superior de Investigaciones Cientificas, E-28002, Madrid, Spain
3 Inserm, U45; Lyon, IFR62; University Claude Bernard Lyon I, Faculte de Medecine R. Laennec, Lyon, F-69327, France; Inra, laboratoire d'Ecologie et de Physiologie du Systeme Digestif (UEPSD), Jouy en Josas, France
* To whom correspondence should be addressed. E-mail: plaisancie{at}lyon.inserm.fr.
We recently showed that
-casomorphin-7, a milk opioid peptide, strongly stimulates mucin secretion in rat jejunum through a nervous pathway and opioid receptor activation. In this study, the hypothesis that
-casomorphin-7 may also act directly on intestinal goblet cells was investigated in vitro in rat and human intestinal mucin-producing cells (DHE and HT29-MTX) using quantitative and semi-quantitative RT-PCR and ELISA. The presence of µ-opioid receptors was demonstrated in rat goblet cells in the upper half of the colonic crypt and in the two cell lines by immunohistochemistry and RT-PCR. In rat DHE cells,
-casomorphin-7 increased the expression of rMuc2 and rMuc3 but not of rMuc1, rMuc4 and rMuc5AC. This effect was time- and dose-dependent, the maximum of increase in transcripts being noticed for a concentration of 10-4 mol/L after 2 hours of stimulation for rMuc2 (225 % of controls) and 4 hours of stimulation for rMuc3 (208 % of controls). Mucin secretion was maximally increased after 8 hours of stimulation. Interestingly, these effects were prevented by pre-treatment of the cells with the µ-opioid antagonist cyprodime. In human HT29-MTX cells,
-casomorphin-7 (10-4 mol/L) also increased MUC5AC mRNA levels (219% after 24 hours of stimulation) and the secretion of this mucin (169% of controls). In conclusion,
-casomorphin-7 may contribute significantly to mucin production via a direct effect on intestinal goblet cells and the activation of µ-opioid receptors. Since intestinal mucins have a crucial mucosal protective function, dairy products containing
-casomorphin-7 may improve intestinal protection and could have dietary and health applications.
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