AQP and the control of fluid transport in a salivary gland.

Experiments were performed with the perfused rat submandibular gland in vitro to investigate the nature of the coupling between transported salt and water by varying the osmolarity of the source bath and observing the changes in secretory volume flow. Glands were submitted to hypertonic step changes by changing the saline perfusate to one containing different levels of sucrose. The flow rate responded by falling to a lower value, establishing a new steady-state flow. The rate changes did not correspond to those expected from a system in which fluid production is due to simple osmotic equilibration, but were much larger. The changes were fitted to a model in which fluid production is largely paracellular, the rate of which is controlled by an osmosensor system in the basal membrane. The same experiments were done with glands from rats that had been bred to have very low levels of AQP5 (the principal aquaporin of the salivary acinar cell) in which little AQP5 is expressed at the basal membrane. In these rats, salivary secretion rates after hypertonic challenges were small and best modelled by simple osmotic equilibration. In rats which had intermediate AQP5 levels the changes in flow rate were similar to those of normal rats although their AQP5 levels were reduced.Finally, perfused normal glands were subject to retrograde ductal injection of salines containing different levels of Hg(2+) ions (0, 10 and 100 microM: ) which would act as inhibitors of AQP5 at the apical acinar membrane. The overall flow rates were progressively diminished with rising Hg(2+) concentration, but after hypertonic challenge the changes in flow rates were unchanged and similar to those of normal rats. All these results are difficult to explain by a cellular osmotic model but can be explained by a model in which paracellular flow is controlled by an osmosensor (presumably AQP5) present on the basal membrane.