During lactation, increased food intake results in the increased intake of contaminating chemicals/toxins, which increases the capacity of the intestinal tract to secrete conjugated xenobiotics and resorb bile salts. Villanueva et al. investigated the coordinated regulation of conjugating enzymes and multidrug resistance-associated protein 2 (Mrp2) and the potential hormonal factors that increase the activity of these systems. Glucagon-like peptide 2 (GLP-2) expression increases during lactation, and its receptor is highly expressed in the jejunum where significant expression of Mrp2 has been observed. Administration of GLP-2 results in the induction and expression of Mrp2 and the specific α isoform of glutathione transferase, GSTYa2, in rat jejunum. Treatment of rats with 2′,3′dideoxyadenosine, a specific adenylyl cyclase inhibitor, abolished increased cAMP levels in the intestine and the expression of Mrp2 induced by GLP-2. This is the first demonstration of a role for GLP-2 in regulating expression and activity of jejunal Mrp2 and an indication that this regulation is through activation of adenylyl cyclase. This study suggests a role for GLP-2 in the prevention of cellular toxicity under conditions of intestinal damage or as a complement to its trophic actions during development, lactation, or tissue regeneration.
See article at J Pharmacol Exp Ther 2010, 335:332–341.
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