Fluid and HCO₃⁻secretion is a vital function of all epithelia and is required for the survival of the tissue. Aberrant fluid and HCO₃⁻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 HCO₃⁻secretion, in particular by secretory glands. Fluid and HCO₃⁻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⁻and secrete HCO₃⁻. 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⁻and secretes HCO₃⁻and the bulk of the fluid in the pancreatic juice. Fluid secretion appears to be driven by active HCO₃⁻secretion. In the salivary glands, acinar cells secrete the bulk of the fluid in the saliva that is driven by active Cl⁻secretion and contains high concentrations of Na⁺and Cl⁻. The salivary glands duct absorbs both the Na⁺and Cl⁻and secretes K⁺and HCO₃⁻. In this review, we focus on the molecular mechanism of fluid and HCO₃⁻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.

Transepithelial Cl⁻and HCO₃⁻transport is critically important for the function of all epithelia and, when altered or ablated, leads to a number of diseases, including cystic fibrosis, congenital chloride diarrhea, deafness, and hypotension ( 78 , 111 , 119 , 126 ). HCO₃⁻is the biological buffer that maintains acid-base balance, thereby preventing metabolic and respiratory acidosis ( 48 ). HCO₃⁻also buffers the pH of the mucosal layers that line all epithelia, protecting them from injury ( 2 ). Being a chaotropic ion, HCO₃⁻is essential for solubilization of ions and macromolecules such as mucins and digestive enzymes in secreted fluids. Most epithelia have a Cl⁻/HCO₃exchange activity in the luminal membrane. The molecular nature of this activity remained a mystery for many years until the discovery of SLC26A3 and the realization that it is a member of a new family of Cl⁻and HCO₃⁻transporters, the SLC26 family ( 73 , 78 ). This review will highlight structural features, the functional diversity, and several regulatory aspects of the SLC26 transporters.

We investigated which transient receptor potential (TRP) channel is responsible for the nonselective cation channel (NSCC) activated by carbachol (CCh) in murine stomach with RT-PCR and the electrophysiological method. All seven types of TRP mRNA were detected in murine stomach with RT-PCR. When each TRP channel was expressed, the current-voltage relationship of mTRP5 was most similar to that recorded in murine gastric myocytes. mTRP5 showed a conductance order of Cs⁺> K⁺> Na⁺, similar to that in the murine stomach. With 0.2 mM GTPγS in the pipette solution, the current was activated transiently in both NSCC in the murine stomach and the expressed mTRP5. Both NSCC activated by CCh in murine stomach and mTRP5 were inhibited by intracellularly applied anti-G_q/11antibody, PLC inhibitor U-73122, IICR inhibitor 2-aminoethoxydiphenylborate, and nonspecific cation channel blockers La³⁺and flufenamate. There were two other unique properties. Both the native NSCC and mTRP5 were activated by 1-oleoyl-2-acetyl-sn-glycerol. Without the activation of NSCC by CCh, the NSCC in murine stomach was constitutively active like mTRP5. From the above results, we suggest that mTRP5 might be a candidate for the NSCC activated by ACh or CCh in murine stomach.