Nonoguchi H, Owada A, Kobayashi N, Takayama M, Terada Y, Koike J, Ujiie K, Marumo F, Sakai T, Tomita K
Third Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
J Clin Invest. 1995 Oct;96(4):1768-78. doi: 10.1172/JCI118222.
We investigated immunohistochemical localization of V2 vasopressin receptor along the nephron using a specific polyclonal antibody. Staining was observed in some of thick ascending limbs and all of principal and inner medullary collecting duct (IMCD) cells. Not only basolateral but also luminal membrane was stained in collecting ducts, especially in terminal IMCD (tIMCD). To learn the functional role of luminal V2 receptor in tIMCD, we studied the luminal effects of arginine vasopressin (AVP) on osmotic water permeability (Pf), urea permeability (Pu), and cAMP accumulation using isolated perfused rat tIMCD. In the absence of bath AVP, luminal AVP caused a small increase in cAMP accumulation, Pf and Pu, confirming the presence of V2 receptor in the lumen of tIMCD. In contrast, luminal AVP inhibited Pf and Pu by 30-65% in the presence of bath AVP by decreasing cAMP accumulation via V1a or oxytocin receptors and by an unknown mechanism via V2 receptors in the luminal membrane of tIMCD. These data show that V2 receptors are localized not only in the basolateral membrane but also in the luminal membrane of the distal nephron. Luminal AVP acts as a negative feedback system upon the basolateral action of AVP in tIMCD.
我们使用特异性多克隆抗体研究了血管升压素V2受体在肾单位中的免疫组化定位。在一些髓袢升支粗段以及所有的主细胞和内髓集合管(IMCD)细胞中均观察到染色。在集合管中,不仅基底外侧膜,而且管腔膜也被染色,尤其是在终末IMCD(tIMCD)中。为了解管腔V2受体在tIMCD中的功能作用,我们使用分离灌注的大鼠tIMCD研究了精氨酸血管升压素(AVP)对渗透水通透性(Pf)、尿素通透性(Pu)和环磷酸腺苷(cAMP)积累的管腔效应。在浴槽中不存在AVP的情况下,管腔AVP导致cAMP积累、Pf和Pu略有增加,证实了tIMCD管腔中存在V2受体。相反,在浴槽中存在AVP的情况下,管腔AVP通过V1a或催产素受体降低cAMP积累,并通过tIMCD管腔膜中V2受体的未知机制,使Pf和Pu抑制30 - 65%。这些数据表明,V2受体不仅定位于远端肾单位的基底外侧膜,也定位于管腔膜。管腔AVP对tIMCD中AVP的基底外侧作用起负反馈系统的作用。