The electrolyte/fluid secretion stimulatory peptides guanylin and uroguanylin and their common functional coupling proteins in the rat pancreas: a correlative study of expression and cell-specific localization.

INTRODUCTION: Guanylin and uroguanylin are intestinal or urine peptides that stimulate epithelial electrolyte/fluid secretion by activating the cystic fibrosis gene product (CFTR). AIMS: Because CFTR is essentially involved in the electrolyte secretion of the pancreatic duct cells, the rat pancreas was investigated for expression and cell-specific localization of guanylin and uroguanylin; expression of major components of the guanylin signaling pathway, i.e., the guanylin/uroguanylin receptor guanylate cyclase C (GC-C), cGMP-dependent protein kinase II, and CFTR; and expression of the epithelial Cl-/HCO3- exchanger AE2. METHODOLOGY AND
RESULTS: Reverse transcriptase polymerase chain reaction analyses revealed high expression of guanylin, uroguanylin, and the functional coupling proteins in the rat pancreas. At the cellular level, guanylin and uroguanylin were localized by immunohistochemistry to the centroacinar cells and proximal duct cells of the exocrine pancreas. The guanylin/uroguanylin receptor GC-C, cGKII, CFTR, and AE2 were all found in the same segments of the ductal system, where they were confined to the apical membrane of centroacinar cells and proximal duct epithelial cells, a circumstance suggesting that both peptides may act through the ductal lumen.
CONCLUSION: In view of the well-known functional significance of guanylin and uroguanylin, the presence and cell-specific expression not only of the both peptides but also of their common functional coupling proteins implicates a regulatory function of these peptides in the electrolyte/fluid secretion within the rat exocrine pancreas.