PAR-2 and protective gastric secretion

Kawabata and colleagues have shown previously that the protease-activated receptor PAR-2, which is expressed in sensory neurons throughout the gastrointestinal tract and elsewhere, activates secretion by the salivary gland and the exocrine pancreas. This receptor, which may be best known for its ability to induce smooth muscle relaxation in the vasculature and bronchioles, is unusual in that it carries its own ligand as part of its sequence. As the name suggests, proteolytic cleavage of the receptor frees the ligand to bind and activate the receptor, so PAR-2 signaling normally depends on the presence of trypsin or other proteinases, but it can be stimulated artificially by providing the activating sequence in a synthetic peptide. Here, Kawabata et al. show that such peptides can stimulate sensory nerves in the stomach and activate the secretion of gastric mucus. As expected, given the presumed protective role of this mucus, PAR-2 agonists block erosion of the stomach lining in rats with high levels of gastric acid. This finding may point the way to useful preventative treatments for gastric ulcers, including those that result from heightened acid secretion caused by chronic use of aspirin or other common analgesics.