HUMAN SPASMOLYTIC POLYPEPTIDE DECREASES PROTON PERMEATION THROUGH GASTRIC MUCUS IN-VIVO AND IN-VITRO

Exogenously administered trefoil peptides are gastroprotective in rat injury models. We hypothesized that trefoil-associated gastroprotectio n occurred by decreasing the rate of proton permeation through mucus. Gastric surface cell intracellular pH and mucus gel thickness were mea sured by in vivo microscopy. Gastric mucosal blood flow was measured b y laser-Doppler flowmetry. The effect of human spasmolytic peptide (hS P) on H+ diffusion through 5% purified porcine mucin was measured usin g an Ussing chamber. Buffering action of mucin was measured by titrati on. In vivo, gastric mucosal blood flow and mucus gel thickness were n ot affected by any of the treatments. Topical hSP, but not intravenous hSP, decreased initial acidification rate and elevated the intracellu lar pH of gastric surface cells during luminal acid challenge. In in v itro studies, hSP dose dependently decreased the diffusion coefficient of H+ through 5% porcine mucin solution. hSP had no significant effec t on the buffering action of mucin solutions. These data support our h ypothesis that hSP interacts with gastric mucin in a manner that inhib its proton permeation through the mucus gel layer.