TRPV4 activation in mouse submandibular gland modulates Ca2+ influx and salivation.
TRPV4 activation in mouse submandibular gland modulates Ca2+ influx and salivation.
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小鼠颌下腺中 TRPV4 的激活调节 Ca2 流入和唾液分泌。
DOI：
10.1152/ajpgi.00366.2012
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Melvin,JamesE
中科院分区：
文献类型：
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作者：
Zhang,Yan;Catalan,MarceloA;Melvin,JamesE
瞬时受体电位香草亚型4(TRPV4)是一种配体门控的非选择性阳离子通道，参与机械刺激和渗透刺激在不同组织中的传递。内源性花生四烯酸代谢产物、4-α-佛波醇-12，13-十二酸、GSK1016790A、中温和机械应激均可激活TRPV4。TRPV4在唾液腺中表达，但其表达模式和功能尚不清楚。本研究的目的是评价TRPV4通道在小鼠颌下腺中的功能作用。通过RT-PCR和Western印迹分析，我们分别检测了TRPV4基因在颌下腺中的表达。免疫定位研究表明，TRPV4靶向于小鼠颌下腺腺泡细胞的基底膜。使用选择性激动剂GSK1016790A的药物激活TRPV4导致分离的腺泡细胞中的钙离子以基波到尖波的形式内流。与这些观察结果一致的是，GSK1016790A在依赖细胞外钙离子的颌下腺中诱导了唾液分泌。综上所述，我们报道了TRPV4通道的激活诱导了钙离子内流和唾液分泌，从而可能在小鼠颌下腺中贡献了一种新的非肾上腺素、非胆碱能分泌途径。
Transient receptor potential vanilloid subtype 4 (TRPV4) is a ligand-gated nonselective cation channel that participates in the transduction of mechanical and osmotic stimuli in different tissues. TRPV4 is activated by endogenous arachidonic acid metabolites, 4α-phorbol-12,13 didecanoate, GSK1016790A, moderate heat, and mechanical stress. TRPV4 is expressed in the salivary glands, but its expression pattern and function are poorly understood. The aim of this study was to evaluate the functional role of TRPV4 channels in the mouse submandibular gland. Using RT-PCR and Western blot analysis, we detected expression of TRPV4 message and protein, respectively, in the submandibular gland. Immunolocalization studies showed that TRPV4 targeted to the basolateral membrane of mouse submandibular gland acinar cells. Pharmacological TRPV4 activation using the selective agonist GSK1016790A caused Ca2+influx in isolated acinar cells in a basal-to-apical wave. Consistent with these observations, GSK1016790A elicited salivation in the perfused submandibular gland that was dependent on extracellular Ca2+. In summary, we report that activation of TRPV4 channels induced Ca2+influx and salivation and, thus, may contribute a novel nonadrenergic, noncholinergic secretion pathway in the mouse submandibular gland.