Effect of sucralfate on components of mucosal barrier produced by cultured canine epithelial cells in vitro

The mucous gel maintains a neutral microclimate at the epithelial cell surface, which may play a role in both the prevention of gastroduodenal injury and the provision of an environment essential for epithelial restitution and regeneration after injury. Enhancement of the components of the mucous barrier by sucralfate may explain its therapeutic efficacy for upper gastrointestinal tract protection, repai, and healing. We studied the effect of sucralfate and its major soluble component, sucrose octasulfate (SOS), on the synthesis and release of gastric mucin and surface active phospholipid, utilizing an isolated canine gastric mucous cells in culture. We correlated these results with the effect of the agents on mucin synthesis and secretion utilizing explants of canine fundus in vitro . Sucralfate and SOS significantly stimulated phospholipid secretion by isolated canine mucous cells in culture (123% and 112% of control, respectively.) Indomethacin pretreatment siginificantly inhibited the effect of sucralfate, but not SOS, on the stimulation of phospholipid release. Administration of either sucralfate or SOS to the isolated canine mucous cells had no effect upon mucin synthesis or secretion using a sensitive immunoassay. Sucralfate and SOS did not stimulate mucin release in the canine explants; sucralfate significantly stimulated the synthesis of mucin, but only to 108% of that observed in untreated explants. No increase in PGE 2 release was observed after sucralfate or SOS exposure to the isolated canine mucous cells. Our results suggest sucralfate affects the mucus barrier largely in a qualitative manner. No increase in mucin secretion or major effect on synthesis was notd, although a significant increase in surface active phospholipid release was observed. The lack of dose dependency of this effect, along with the results of the PGE 2 assay, suggests the drug may act through a non-receptor-mediated mechanism to perturb the cell membrane and release surface active phospholipid. The enhancement of phospholipid release by sucralfate to augment the barrier function of gastric mucus may, in concert with other effects of the drug, strrengthen mucosal barrier function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44415/1/10620_2005_Article_BF01308079.pd