Vasotocin and vasopressin stimulation of the chloride secretion in the human bronchial epithelial cell line, 16HBE14o-
Vasotocin and vasopressin stimulation of the chloride secretion in the human bronchial epithelial cell line, 16HBE14o-
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DOI：
10.1038/sj.bjp.0706103
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发表时间：
2005-04-01
影响因子：
7.3
通讯作者：
Ehrenfeld, J
中科院分区：
文献类型：
--
作者：
Bernard, K;Bogliolo, S;Ehrenfeld, J
抗利尿激素家族神经肽对肺中Cl-分泌的影响尚未见报道。利用16HBE14o-支气管上皮细胞系，我们研究了它们对Cl-分泌的作用在对称Cl-溶液中，基底侧应用精氨酸血管催产素（AVT）、催产素或异催产素诱导短暂的I-sc刺激（i -峰），而精氨酸血管加压素（AVP）则没有。不同的Cl-通道阻滞剂和PKC抑制剂的作用表明CFTR参与了i -峰。钙活化的K+通道（SK4）和Cl-/HCO3-交换有利于avt介导的Cl-分泌的驱动力。V1a (SR49059)-和V1b (SSR149415)-受体拮抗剂阻断i -峰，而V2受体拮抗剂SR121463B没有阻断i -峰。这些结果表明，刺激一个v1样受体介导I-sc峰，并呈现出一个作用顺序，AVT >催产素>异催产素>> AVP.3当应用浆膜到粘膜Cl-梯度时，AVT和AVP均根据双相曲线刺激I-sc， i -峰值之后是平台期（I-plateau）。i -平台的药理学表明CFTR通道参与其中，Na+/K+/2Cl（-）是唯一与i -平台相关的转运体。dDAVP是一种V2受体激动剂诱导的i -平台，其效力与AVP相同，表明V2受体参与了AVP诱导的i -平台。V2受体存在于相对膜上，而v1样受体主要表达于基底外侧膜上。RT-PCR实验显示V1a、V1b、V2和抗利尿激素激活的钙动员受体mrna均有表达。
1 Effects of neuropeptides of the vasopressin family on Cl- secretion have not yet been reported in lung. Using the 16HBE14o- bronchial epithelial cell line, we investigated their action on Cl- secretion.2 In symmetrical Cl- solutions, basolateral application of arginine vasotocin (AVT), oxytocin or isotocin induced a transient I-sc stimulation (I-peak), whereas arginine vasopressin (AVP) did not. The effects of different Cl- channel blockers and of a protein kinase C (PKC) inhibitor suggest that CFTR is involved in I-peak. The calcium-activated K+ channel (SK4) and the Cl-/HCO3- exchanger favor the driving force for AVT-mediated Cl- secretion. The antagonists of V1a (SR49059)- and V1b (SSR149415)-receptors blocked I-peak, while SR121463B, a V2 receptor antagonist, did not. These results point to the stimulation of a V1-like receptor mediating I-peak and presenting an efficacy order, AVT > oxytocin > isotocin >> AVP.3 When a serosal to mucosal Cl- gradient was applied, AVT and AVP both stimulated I-sc according to a biphasic profile, I-peak being followed by a plateau phase (I-plateau). The pharmacology of I-plateau suggests that CFTR channels are involved and that Na+/K+/2Cl(-) is the only transporter associated with I-plateau. dDAVP, a V2 receptor agonist-induced I-plateau with the same potency as AVP, suggesting the involvement of V2 receptors in the AVP-induced I-plateau. V2 receptors are present on both opposite membranes, while V1-like receptors are mainly expressed on the basolateral membranes. RT-PCR experiments show the expression of V1a, V1b, V2 and vasopressin-activated calcium-mobilizing ( VACM) receptors mRNAs.