Molecular Mechanism of Pancreatic and Salivary Gland Fluid and HCO₃⁻Secretion

Abstract

<jats:p>Fluid and HCO<jats:sub>3</jats:sub><jats:sup>−</jats:sup>secretion is a vital function of all epithelia and is required for the survival of the tissue. Aberrant fluid and HCO<jats:sub>3</jats:sub><jats:sup>−</jats:sup>secretion is associated with many epithelial diseases, such as cystic fibrosis, pancreatitis, Sjögren's syndrome, and other epithelial inflammatory and autoimmune diseases. Significant progress has been made over the last 20 years in our understanding of epithelial fluid and HCO<jats:sub>3</jats:sub><jats:sup>−</jats:sup>secretion, in particular by secretory glands. Fluid and HCO<jats:sub>3</jats:sub><jats:sup>−</jats:sup>secretion by secretory glands is a two-step process. Acinar cells secrete isotonic fluid in which the major salt is NaCl. Subsequently, the duct modifies the volume and electrolyte composition of the fluid to absorb the Cl<jats:sup>−</jats:sup>and secrete HCO<jats:sub>3</jats:sub><jats:sup>−</jats:sup>. The relative volume secreted by acinar and duct cells and modification of electrolyte composition of the secreted fluids varies among secretory glands to meet their physiological functions. In the pancreas, acinar cells secrete a small amount of NaCl-rich fluid, while the duct absorbs the Cl<jats:sup>−</jats:sup>and secretes HCO<jats:sub>3</jats:sub><jats:sup>−</jats:sup>and the bulk of the fluid in the pancreatic juice. Fluid secretion appears to be driven by active HCO<jats:sub>3</jats:sub><jats:sup>−</jats:sup>secretion. In the salivary glands, acinar cells secrete the bulk of the fluid in the saliva that is driven by active Cl<jats:sup>−</jats:sup>secretion and contains high concentrations of Na<jats:sup>+</jats:sup>and Cl<jats:sup>−</jats:sup>. The salivary glands duct absorbs both the Na<jats:sup>+</jats:sup>and Cl<jats:sup>−</jats:sup>and secretes K<jats:sup>+</jats:sup>and HCO<jats:sub>3</jats:sub><jats:sup>−</jats:sup>. In this review, we focus on the molecular mechanism of fluid and HCO<jats:sub>3</jats:sub><jats:sup>−</jats:sup>secretion by the pancreas and salivary glands, to highlight the similarities of the fundamental mechanisms of acinar and duct cell functions, and to point out the differences to meet gland-specific secretions.</jats:p>

A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland

“…The Cl − dependency of IPR-induced fluid secretion is in agreement with the current model for saliva secretion; that is, the secretory machinery is composed of basolateral Cl − uptake and apical Cl − efflux pathways. In contrast, the HCO 3 − dependency suggests either that the basolateral Cl − uptake pathway depends markedly on HCO 3 − ions or that HCO 3 − secretion may be linked to fluid secretion. Future experiments are needed to acquire more insight into the mechanism by which HCO 3 − modulates IPR-induced salivary gland fluid secretion.…”

“…The major ion-transporting proteins involved in fluid secretion have been identified in exocrine glands (1,3). It was recently proposed in salivary glands that Tmem16A (4-6) encodes the apical Ca 2+ -activated Cl − channel (CaCC) efflux pathway required for Ca 2+ -dependent fluid secretion (6,7), whereas the molecular identity of the apical Cl − efflux pathway involved in β-adrenergic receptor-activated secretion is unknown.…”

Aquaporin gene therapy corrects Sjögren’s syndrome phenotype in mice

“…Initiation of fluid secretion in the salivary gland requires movement of water and ions through their respective channels in the acinar cells (reviewed in ref. 17). AQP5 is the main water channel for salivary fluid secretion (reviewed in ref.…”

SLC26A6 and NaDC-1 Transporters Interact to Regulate Oxalate and Citrate Homeostasis

“…4 Slc26a6 is expressed at high levels in most epithelia, including the proximal intestine, renal proximal tubule, salivary glands, and pancreas. 5 Slc26a6 functions as a 1Cl 2 /2HCO 3 6 or 1Cl 2 /1oxalate and 1Cl 2 /1for-mate exchanger. 7 Its pivotal role in oxalate homeostasis was demonstrated in slc26a6 2/2 mice, where the most prominent phenotype is increased serum and urine oxalate that lead to Ca 2+ -oxalate kidney stones.…”