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Possible role of oxytocin receptor as a mediator of vasopressin action in the kidney

催产素受体作为肾脏加压素作用介质的可能作用

基本信息

批准号：
12671044
负责人：
ANDO Yasuhiro
金额：
$ 1.98万
依托单位：
Jichi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671044/
关键词：
vasopressin oxytocin collecting duct thick ascending loop of Henle cyclic GMP uroguanylin protein kinase C Ca ionophore 髄質部ヘンレの太い上行脚ラットマウスヘンレの太い上行脚ナトリウム輸送

项目摘要

1. Effect of oxytocin (OT) in the rabbit cortical collecting ductBasolateral OT mimiced the effect of vasopressin V2 recetpor on transepithelial voltage (Vt) and osmotic permeeability in the rabbit CCD. However, these were considered to be mediated via basolateral V2 receptor but not OT receptor, since a specific OT agonist failed to reproduce these effects and V1 antagonist was unable to suppress these reactions.2. Screening of tubular effect of OT by using several second messenger analonues.1) cyclic GMP system : In cortical and medullary thick ascending limb (CAL and MAL, respectively), CCD, outer medullary and innner collecting duct (OMCD and IMCD, respectively) of the rabbit, uroguanylin had no effecton Vt.8-bromo-cGMP was inert in MAL as well. Though 8-Br-cGMP mimiced the effect of V2 receptor on Vt and water transport in the CCD, it appeared to be the cross-reaction to activate cAMP system instead of specific cGMP-mediated event.2) intracellular Ca++ and protein kinase C (PKC) systems : The Ca-ionophore ionomycin stimulated Cl transport in rat MAL while suppresssed JCl in mouse MAL. PKC did not alter JCl in MAL of both species. Indomethacin pretreatment mitigated the ionomycin-induced suppression of JCl in the mouse, while the elevation of JCl in rat MAL was not changed. In mouse MAL, thus, elevation of intracellular Ca++ was thought to be inhibitory to Cl transport in mouse MAL and this effect is, in part, prostaglandin dependent. On the other hand, elevation of intracellular Ca++ may employ distinct signalling network system in enhancing JCl in rat MAL.3. SummaryThese exploration implies that OT receptor is unlikely to be a n important mediator of vasopressin action in the collectong duct. However, it is to be evatulated further that, in MAL, OT receptor, if any, may mediate the vasopressin actions via intracellular Ca++ system in a species-dependent manner.

1. 垂体后叶催产素（OT）对兔皮质集管的影响基底外侧垂体后叶催产素模拟加压素V2受体对兔CCD上皮传导电压（Vt）和渗透通透性的影响。然而，这些被认为是通过基底外侧V2受体而不是OT受体介导的，因为特定的OT激动剂无法复制这些作用，V1拮抗剂无法抑制这些反应。利用几种第二信使模拟物筛选OT的管状效应。1)循环GMP系统：在兔皮质和髓质厚升肢（CAL和MAL）、CCD、髓外和内集管（OMCD和IMCD）中，尿观音林无作用，8-溴- cgmp在MAL中也无活性。虽然8-Br-cGMP模拟了V2受体对CCD内Vt和水转运的影响，但它似乎是激活cAMP系统的交叉反应，而不是cgmp介导的特异性事件。2)细胞内Ca++和蛋白激酶C （PKC）系统：钙离子离子离子素刺激大鼠MAL中Cl的转运，抑制小鼠MAL中JCl的转运，PKC未改变两种动物MAL中JCl的转运。吲哚美辛预处理减轻了离子霉素对小鼠JCl的抑制作用，而对大鼠MAL中JCl的升高没有影响。因此，在小鼠MAL中，细胞内ca2 +的升高被认为抑制了小鼠MAL中Cl的转运，这种作用部分依赖于前列腺素。另一方面，细胞内Ca++的升高可能通过不同的信号网络系统增强了大鼠mal的JCl。这些研究表明，OT受体不太可能是集束管中抗利尿激素作用的重要介质。然而，在MAL中，如果存在OT受体，则可能以物种依赖的方式通过细胞内Ca++系统介导抗利尿激素的作用，这还有待进一步的评估。