Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated secretion of an
electrolyte-rich fluid is a major but incompletely understood function of the salivary glands. We provide molecular evidence that
guanylin, a bioactive intestinal
peptide involved in the CFTR-regulated secretion of
electrolyte/water in the gut epithelium, is highly expressed in the human parotid and submandibular glands and in respective clinically most relevant
tumors. Moreover, in the same organs we identified expression of the major components of the
guanylin signaling pathway, ie,
guanylin-receptor
guanylate cyclase-C, cGKII, and CFTR, as well as of the epithelial Cl(-)/HCO(3)(-)
anion exchanger type 2 (AE2). At the cellular level,
guanylin is localized to epithelial cells of the ductal system that, based on its presence in the saliva, is obviously released into the salivary gland ducts. The
guanylin-receptor
guanylate cyclase-C, cGKII, CFTR, and AE2 are all confined exclusively to the apical membrane of the same duct cells. These findings implicate
guanylin as intrinsic regulator of
electrolyte secretion in the salivary glands. We assume that duct epithelial cells synthesize and release
guanylin into the saliva to regulate
electrolyte secretion in the ductal system by an intraductal luminocrine signaling pathway. Moreover, the high expression of
guanylin in
pleomorphic adenoma and Warthin
tumors (cystadenolymphoma), the most common
neoplasms of salivary glands, predicts
guanylin as a significant marker in
tumor pathology.