Downregulation of vasopressin V2 receptor promoter activity via V1a receptor pathway
Downregulation of vasopressin V2 receptor promoter activity via V1a receptor pathway
复制标题
DOI：
10.1152/ajprenal.00358.2006
复制
发表时间：
2007-05-01
影响因子：
4.2
通讯作者：
Tomita, Kimio
中科院分区：
文献类型：
--
作者：
Izumi, Yuichiro;Nakayama, Yushi;Tomita, Kimio
抗利尿激素V-1a和V-2受体（分别为V1aR和V2R）分布在肾集管中。虽然V2R介导AVP抗利尿作用的功能已被详细研究，但V1aR在集合管中的作用尚未阐明。在本研究中，我们研究了V1aR通路在V2R启动子活性中的作用。我们克隆了大鼠V2R （rV(2)R）的5'侧区，并在转染了主要表达大鼠V1aR (rV(1a)R) （LLC-PK1/rV(1a)R）的LLC-PK1细胞系中研究了rV(2)R启动子的活性。AVP诱导这些细胞中rV(2)R启动子活性短暂升高，随后持续降低。avp诱导的rV(2)R启动子活性的降低被V1aR抑制，而V2R拮抗剂则不受抑制。PMA模拟了rV(2)R启动子活性的降低。相反，8-（4-氯苯基硫磷）- camp增加了rV(2)R启动子活性。这些PMA-和8-（4-氯苯基硫磷）camp诱导的效应在缺乏CAAT和SP1位点的5'侧区缺失部分未观察到。综上所述，1)在LLC-PK1/rV(1a)R细胞中，V2R的表达通过V1aR途径下调，2)V2R的表达通过PMA诱导的PKC途径下调，通过cAMPPKA途径上调。PKC和PKA的这些相反作用似乎是由CAAT和SP1的相同启动子区域调控的。
Vasopressin V-1a and V-2 receptors ( V1aR and V2R, respectively) distribute in the collecting duct of the kidney. Although the function of V2R mediating the antidiuretic effect of AVP has been investigated in detail, the role of V1aR in the collecting ducts has not been elucidated. In the present study, we have investigated the role of the V1aR pathway in V2R promoter activity. We cloned the 5'-flanking region of rat V2R (rV(2)R) and investigated rV(2)R promoter activity in the LLC-PK1 cell line transfected to express rat V1aR (rV(1a)R) dominantly (LLC-PK1/rV(1a)R). AVP induced a transient increase, followed by a sustained decrease, of rV(2)R promoter activity in these cells. This AVP-induced decrease of rV(2)R promoter activity was inhibited by V1aR, but not V2R, antagonist. PMA mimicked this decrease of rV(2)R promoter activity. On the contrary, 8-(4-chlorophenylthio)-cAMP increased rV(2)R promoter activity. These PMA- and 8-(4-chlorophenylthio)cAMP-induced effects were not observed on the deletion segment of the 5'-flanking region lacking CAAT and SP1 sites. In conclusion, 1) expression of the V2R is downregulated via the V1aR pathway in LLC-PK1/rV(1a)R cells, and 2) expression of the V2R is downregulated by the PMA- induced PKC pathway and upregulated by the cAMPPKA pathway. These opposite effects of PKC and PKA appear to be regulated by the same promoter region of CAAT and SP1.