Serosal zinc attenuate serotonin and vasoactive intestinal peptide induced secretion in piglet small intestinal epithelium in vitro

This study addressed the mechanisms by which dietary zinc affects diarrhoea and aimed to study possible interactions between zinc status and the presence of zinc in vitro on secretagogue-induced secretion from piglet intestinal epithelium in Ussing chambers. In addition, it was studied from which side of the epithelium zinc would perform an effect and if copper caused similar effects. Twenty-four piglets (28 days of age) were weaned and fed diets containing 100 or 2500 mg zinc/kg (as ZnO) for 5 or 6 days (12 piglets per group). Intestinal epithelium underwent the following 5 treatments: zinc at the mucosal side (M-Zn), zinc at the serosal side (S-Zn), zinc at both sides (MSZn), copper at both sides (MSCu) or water at both sides (control). Provoked secretion in terms of short circuit responses to serotonin (5-HT) and vasoactive intestinal peptide (VIP) were measured. Zinc at the serosal or both sides of the epithelium reduced the 5-HT induced secretion (P<0.001); however, due to interactions (P=0.05) the effect of zinc in vitro was only present in the ZnO100 group. The secretion caused by VIP was not affected by the diet (P=0.33), but zinc at the serosal side or both sides reduced the response to VIP (P<0.001). Copper reduced the 5-HT and VIP induced secretion to a larger extent than zinc. However, copper also disturbed intestinal barrier function as demonstrated by increased transepithelial conductance and increased short circuit current, which was unaffected by zinc. In conclusion, zinc at the serosal side of piglet small intestinal epithelium attenuated 5-HT and VIP induced secretion in vitro. These in vitro studies indicate that in vivo there will be no positive acute effect of increasing luminal Zn concentration on secretagogue-induced chloride secretion and that zinc status at the serosal side of the epithelium has to be increased to reduce secretagogue-induced chloride secretion and thereby diarrhoea. (C) 2007 Elsevier Inc. All rights reserved.