Jeon Un Sil, Joo Kwon Wook, Na Ki Young, Kim Yon Su, Lee Jung Sang, Kim Jin, Kim Gheun-Ho, Nielsen Søren, Knepper Mark A, Han Jin Suk
Departmentof Internal Medicine, Gyeong-sang National University, Chinju, Korea.
Nephron Exp Nephrol. 2003 Jan;93(1):e36-45. doi: 10.1159/000066651.
The aquaporin-2 (AQP2) water channel is mainly located in the apical plasma membrane of collecting duct epithelial cells, but there has been some evidence of a moderate amount of basolateral localization of AQP2 at least in the inner medullary collecting duct (IMCD). Previous in vitro microperfusion studies showed that oxytocin has an antidiuretic action, most likely mediated by the vasopressin V2 receptor (V2R) in rat IMCD. By using immunohistochemistry in kidneys from male Sprague-Dawley rats, we observed acute effects of oxytocin on AQP2 localization which were prevented by a V2R antagonist. After intraperitoneal administration of oxytocin (10 U), immunohistochemistry of IMCD revealed that AQP2 was shifted from diffuse cytoplasmic localization in controls to the apical and basolateral membrane domains in oxytocin-treated rats. This pattern of AQP2 redistribution was noted in connecting tubule, cortical collecting duct and outer medullary collecting duct as well as in IMCD, although the tendency to basolateral localization was somewhat less. The pretreatment using a V2R antagonist blocked redistribution of AQP2 in response to oxytocin. We conclude that oxytocin induces a V2R-mediated redistribution of AQP2-containing cytoplasmic vesicles to both apical and basolateral plasma membrane domains in rat kidney. Oxytocin may be one of the factors that accounts for vasopressin-independent AQP2 targeting in the kidney.
水通道蛋白2（AQP2）水通道主要位于集合管上皮细胞的顶端质膜，但至少在内髓集合管（IMCD）中已有一些证据表明AQP2存在适量的基底外侧定位。先前的体外微灌注研究表明，催产素具有抗利尿作用，最有可能是由大鼠IMCD中的血管加压素V2受体（V2R）介导的。通过对雄性Sprague-Dawley大鼠肾脏进行免疫组织化学研究，我们观察到催产素对AQP2定位的急性影响，而这种影响可被V2R拮抗剂阻断。腹腔注射催产素（10 U）后，IMCD的免疫组织化学显示，AQP2在对照组中呈弥漫性胞质定位，而在催产素处理的大鼠中则转移至顶端和基底外侧膜结构域。尽管基底外侧定位的趋势稍弱，但在连接小管、皮质集合管、外髓集合管以及IMCD中均观察到了这种AQP2重新分布模式。使用V2R拮抗剂进行预处理可阻断AQP2对催产素的重新分布反应。我们得出结论，催产素可诱导V2R介导的含AQP2的胞质囊泡向大鼠肾脏的顶端和基底外侧质膜结构域重新分布。催产素可能是导致肾脏中AQP2靶向作用不依赖血管加压素的因素之一。
