The Role of Aquaporin Water Channels in Fluid Secretion by the Exocrine Pancreas

Abstract

The mammalian exocrine pancreas secretes a near-isosmotic fluid over a wide osmolarity range. The role of aquaporin (AQP) water channels in this process is now becoming clearer. AQP8 water channels, which were initially cloned from rat pancreas, are expressed at the apical membrane of pancreatic acinar cells and contribute to their osmotic permeability. However, the acinar cells secrete relatively little fluid and there is no obvious defect in pancreatic function in AQP8 knockout mice. Most of the fluid secreted by the pancreas is generated by ductal epithelial cells, which comprise only a small fraction of the gland mass. In the human pancreas, secretion occurs mainly in the intercalated ducts, where the epithelial cells express abundant AQP1 and AQP5 at the apical membrane and AQP1 alone at the basolateral membrane. In the rat and mouse, fluid secretion occurs mainly in the interlobular ducts where AQP1 and AQP5 are again co-localized at the apical membrane but appear to be expressed at relatively low levels. Nonetheless, the transepithelial osmotic permeability of rat interlobular ducts is sufficient to support near-isosmotic fluid secretion at observed rates. Furthermore, apical, but not basolateral, application of Hg(2+) significantly reduces the transepithelial osmotic permeability, suggesting that apical AQP1 and AQP5 may contribute significantly to fluid secretion. The apparently normal fluid output of the pancreas in AQP1 knockout mice may reflect the presence of AQP5 at the apical membrane.

Vectorial Bicarbonate Transport by Capan-1 Cells: a Model for Human Pancreatic Ductal Secretion

“…The presence of NKCC1 in these cells is somewhat surprising given that Na + -coupled Cl -uptake at the basolateral membrane would provide a driving force for apical secretion of Cl -and this is thought to be incompatible with the secretion of a HCO 3 --rich juice [34]. Its presence in Capan-1 cells may, however, reflect the origin of these cells in the larger ducts of the human pancreas [35], where the expression levels of the basolateral transporters may differ from those in the smaller intercalated and intralobular ducts that are thought to secrete most of the HCO 3 --rich fluid [5,36]. As far as HCO 3 -secretion is concerned, we have shown that in Capan-1 cells the basolateral NHE and NBC are the main transporters involved in the accumulation of intracellular HCO 3 -for subsequent secretion across the apical membrane.…”

The Protein Kinase A Pathway Contributes to Hg2+-Induced Alterations in Phosphorylation and Subcellular Distribution of Occludin Associated with Increased Tight Junction Permeability of Salivary Epithelial Cell Monolayers

“…Efforts to quantitatively measure water transport in cells have relied substantially on the use of heavy metal ions such as Hg 2ϩ , which are known to inhibit many aquaporins at micromolar concentrations by cross-linking cysteine residues in the watertransporting pore of the channel (Macey, 1984;Preston et al, 1993;Savage and Stroud, 2007). Despite the fact that Hg 2ϩ ions can possibly cross-link cysteine residues in a potentially larger number of cell proteins, inhibition of water transport by Hg 2ϩ ions has evolved into a benchmark for transcellular water transport through epithelial and endothelial cells (Folkesson et al, 1994;Roberts et al, 1994;Schnitzer and Oh, 1996;Ko et al, 2002;Burghardt et al, 2006;Yang et al, 2006).…”

Pregnant phenotype in aquaporin 8-deficient mice

“…Importantly, previous studies [26,28] on AQP8-KO mice have shown that the number, survival, and growth of offspring, as well as urinary concentrating ability, salivary gland fluid secretion ability, pancreatic function and organ weight, do not differ in comparison to wild type mice, with the notable exception of increased testicular weight in AQP8 null mice. Further, osmotically driven water transport, active fluid absorption, Figure 2.…”