title: Desipramine inhibits salivary Ca(2+) signaling and aquaporin translocation.
abstract: OBJECTIVE
  Desipramine 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 Ca(2+) signaling.
  
  
  METHODS
  Cytosolic free Ca(2+) concentration ([Ca(2+) ]i ) was determined with the fluorescent Ca(2+) indicator fura-2/AM. Aquaporin translocation was analyzed by Western blotting and immunocytochemistry of confocal microscopy.
  
  
  RESULTS
  Desipramine inhibited the carbachol- and histamine-mediated increase in cytosolic Ca(2+) ([Ca(2+) ]i ) in a concentration-dependent manner. However, desipramine did not affect increases in [Ca(2+) ]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 [Ca(2+) ]i . We also found that desipramine inhibits the increase in membrane aquaporin-5 level triggered by carbachol and histamine treatments.
  
  
  CONCLUSIONS
  These results imply that desipramine blocks muscarinic and histamine receptor-mediated Ca(2+) signaling and the subsequent translocation of aquaporin-5 in human salivary gland cells, suggesting a novel mechanism for the xerogenic effects of desipramine.
authors: Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors: K
authors: K
authors: Lee
authors: S
authors: S
authors: Choi
authors: L-M
authors: LM
authors: Choi
authors: J
authors: J
authors: Lee
authors: J H
authors: JH
authors: Kim
authors: G
authors: G
authors: Chung
authors: G
authors: G
authors: Lee
authors: S-Y
authors: SY
authors: Choi
authors: K
authors: K
authors: Park
mesh_terms: D051402:Aquaporin 5 / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D006801:Humans; D012469:Salivary Glands / Q000187:drug effects* / Q000378:metabolism
chemical_list: D051402:Aquaporin 5; D002118:Calcium; D003891:Desipramine
keywords: Ca2+ signaling; G-protein-coupled receptor; aquaporin-5; desipramine; salivary gland; salivary secretion