Mechanisms Underlying Activation of α1-Adrenergic Receptor-Induced Trafficking of AQP5 in Rat Parotid Acinar Cells under Isotonic or Hypotonic Conditions

Abstract

Defective cellular trafficking of aquaporin-5 (AQP5) to the apical plasma membrane (APM) in salivary glands is associated with the loss of salivary fluid secretion. To examine mechanisms of α1-adrenoceptor (AR)-induced trafficking of AQP5, immunoconfocal microscopy and Western blot analysis were used to analyze AQP5 localization in parotid tissues stimulated with phenylephrine under different osmolality. Phenylephrine-induced trafficking of AQP5 to the APM and lateral plasma membrane (LPM) was mediated via the α1A-AR subtype, but not the α1B- and α1D-AR subtypes. Phenylephrine-induced trafficking of AQP5 was inhibited by ODQ and KT5823, inhibitors of nitric oxide (NO)-stimulated guanylcyclase (GC) and protein kinase (PK) G, respectively, indicating the involvement of the NO/ soluble (c) GC/PKG signaling pathway. Under isotonic conditions, phenylephrine-induced trafficking was inhibited by La3+, implying the participation of store-operated Ca2+ channel. Under hypotonic conditions, phenylephrine-induced trafficking of AQP5 to the APM was higher than that under isotonic conditions. Under non-stimulated conditions, hypotonicity-induced trafficking of AQP5 to the APM was inhibited by ruthenium red and La3+, suggesting the involvement of extracellular Ca2+ entry. Thus, α1A-AR activation induced the trafficking of AQP5 to the APM and LPM via the Ca2+/ cyclic guanosine monophosphate (cGMP)/PKG signaling pathway, which is associated with store-operated Ca2+ entry.

Salivary gland hypofunction in KK‐Ay type 2 diabetic mice

“…c). Conversely, several studies have demonstrated that the increase in [Ca 2+ ] i is associated with AQP5 translocation into the acinar luminal membrane, and impaired AQP5 translocation is induced by diabetes . Thus, the diminished increase in [Ca 2+ ] i in KK‐A y mice found in the present study may affect AQP5 translocation, which, in turn, may result in salivary dysfunction.…”

Effects of oral stimulation with capsaicin on salivary secretion and neural activities in the autonomic system and the brain

“…Collectively, the present study revealed that oral stimulation with capsaicin generates pungent taste (irritating) sensation which leads to increase in beta wave in EEG suggesting attention increase, and it reflexively causes increases in salivary flow and SIgA secretion with simultaneous elevation of sympathetic activities. Since acinar cells of salivary glands express adrenergic receptors as well as cholinergic receptors, sympathetic activation by capsaicin might result in secretions of fluid, SIgA and α-amylase via α- and β-adrenergic receptors 16, 34, 35, 36. For elucidation of precise mechanisms underlying these effects and relationships between salivary changes and neuronal activities, further molecular and physiological studies will be required.…”

Molecular mechanisms governing aquaporin relocalisation

“…abolished by the TRP channel blocker ruthenium red [108], suggesting a requirement for TRP channel activity in the hypotonicity-induced relocalisation of AQP5, similarly to AQP1 in HEK293 cells [37] and AQP4 in primary human astrocytes [6].…”