Reviews of Physiology, Biochemistry and Pharmacology Vol. 170

Péter Hegyi, Michael Wilschanski, Shmuel Muallem, Gergely L. Lukacs, Miklós Sahin-Tóth, Aliye Uc, Michael A. Gray, Zoltán Rakonczay, József Maléth, Gergely Lukacs, Hegyi, Péter, Wilschanski, Michael, Muallem, Shmuel, Lukacs, Gergely L., Sahin-Tóth, Miklós, Uc, Aliye, Gray, Michael A., Rakonczay, Zoltán, Maléth, József

Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that conducts chloride and bicarbonate ions across epithelial cell membranes. Mutations in the CFTR gene diminish the ion channel function and lead to impaired epithelial fluid transport in multiple organs such as the lung and the pancreas resulting in cystic fibrosis. Heterozygous carriers of CFTR mutations do not develop cystic fibrosis but exhibit increased risk for pancreatitis and associated pancreatic damage characterized by elevated mucus levels, fibrosis, and cyst formation. Importantly, recent studies demonstrated that pancreatitis causing insults, such as alcohol, smoking, or bile acids, strongly inhibit CFTR function. Furthermore, human studies showed reduced levels of CFTR expression and function in all forms of pancreatitis. These findings indicate that impairment of CFTR is critical in the development of pancreatitis; therefore, correcting CFTR function could be the first specific therapy in pancreatitis. In this review, we summarize recent advances in the field and discuss new possibilities for the treatment of pancreatitis.