Mechanisms Underlying Activation of 1-Adrenergic Receptor-Induced Trafficking of AQP5 in Rat Parotid Acinar Cells under Isotonic or Hypotonic Conditions
Mechanisms Underlying Activation of 1-Adrenergic Receptor-Induced Trafficking of AQP5 in Rat Parotid Acinar Cells under Isotonic or Hypotonic Conditions
复制标题
DOI：
10.3390/ijms17071022
复制
发表时间：
2016-07-01
影响因子：
5.6
通讯作者：
Ishikawa, Yasuko
中科院分区：
文献类型：
--
作者：
Bragiel, Aneta M.;Wang, Di;Ishikawa, Yasuko
唾液腺中水通道蛋白-5(AQP5)向顶质膜(APM)转运的缺陷与唾液分泌的丧失有关。为探讨(1)肾上腺素受体(AR)介导AQP5转运的机制，应用免疫共聚焦显微镜和Western印迹分析了不同渗透压下苯肾上腺素刺激的腮腺组织中AQP5的定位。苯肾上腺素诱导的AQP5转运是通过(1A)-AR亚型介导的，而不是(1B)-和(1D)-AR亚型介导的。ODQ和KT5823分别被一氧化氮(NO)刺激的鸟苷环酶(GC)和蛋白激酶(PK)G抑制苯肾上腺素诱导的AQP5的转运，表明NO/可溶性(C)GC/PKG信号通路参与了AQP5的转运。在等渗条件下，La3+抑制了苯肾上腺素的转运，提示钙离子通道参与了苯肾上腺素的转运。在低渗条件下，苯肾上腺素诱导的AQP5向APM的转运高于等渗条件。在非刺激条件下，Ru红和La3+可抑制低张诱导的AQP5向APM的转运，提示AQP5参与了细胞外钙内流。因此，(1A)-AR激活诱导AQP5通过钙/环鸟苷一磷酸(CGMP)/PKG信号通路转运到APM和LPM，该信号通路与钙库操作的钙内流有关。
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 (1)-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 (1A)-AR subtype, but not the (1B)- and (1D)-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, (1A)-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.