Inhibition of salivary fluid secretion by occlusion of the intercellular space.

The effects of HCO3- on fluid secretory rate, cell volume and tissue structure were studied in perfused submandibular salivary glands under hyposmotic conditions (240 mosM). Fluid secretion was elicited by acetylcholine (ACh) in a hyposmotic HCO3(-)-free solution. Upon switching the perfusate from the HCO3(-)-free to the HCO3(-)-containing solution during ACh stimulation, the fluid secretory rate exhibited a small transient increase followed by a sharp decrease. ACh stimulation evoked rapid cell shrinkage in the absence of HCO3-, but upon switching from the HCO3(-)-free to the HCO3(-)-containing solution during ACh stimulation, the acinar cells exhibited increases in volume. In laser confocal microscopic examination of isolated acini, fluorescence of lucifer yellow was detected in the lateral intercellular spaces during ACh stimulation in the absence of HCO3-, but not in the presence of HCO3-. Electron microscopic examination revealed similar findings. We propose that the occlusion of the lateral intercellular space induced by cell swelling may result in an increase in the resistance to fluid flow in the space and consequently a decrease in the fluid secretion rate. Maintenance of an open lateral intercellular space may be an important requirement for fluid secretion. These observations suggest that a paracellular pathway may play a significant role in salivary fluid secretion.