Desipramine inhibits salivary Ca(2+) signaling and aquaporin translocation.

ObjectiveDesipramine is a tricyclic antidepressant with a negative side effect of dry mouth. The Na+/H+ exchanger was suggested to be a target of desipramine in salivary gland cells. However, it is unclear whether desipramine has other targets in the salivary secretion pathway. Here, we studied the effect of desipramine on salivary Ca2+ signaling. Materials and MethodsCytosolic free Ca2+ concentration ([Ca2+](i)) was determined with the fluorescent Ca2+ indicator fura-2/AM. Aquaporin translocation was analyzed by Western blotting and immunocytochemistry of confocal microscopy. ResultsDesipramine inhibited the carbachol- and histamine-mediated increase in cytosolic Ca2+ ([Ca2+](i)) in a concentration-dependent manner. However, desipramine did not affect increases in [Ca2+](i) mediated by extracellular ATP, sphingosine-1-phosphate, or thapsigargin. The adrenergic receptor blockers prazosin and propranolol did not reverse the desipramine-mediated inhibition of carbachol- and histamine-induced increases in [Ca2+](i). We also found that desipramine inhibits the increase in membrane aquaporin-5 level triggered by carbachol and histamine treatments. ConclusionsThese results imply that desipramine blocks muscarinic and histamine receptor-mediated Ca2+ signaling and the subsequent translocation of aquaporin-5 in human salivary gland cells, suggesting a novel mechanism for the xerogenic effects of desipramine.