Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct
Apical extracellular calcium/polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct
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DOI：
10.1172/jci119299
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发表时间：
1997-03-15
影响因子：
15.9
通讯作者：
Harris, HW
中科院分区：
文献类型：
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作者：
Sands, JM;Naruse, M;Harris, HW
在抗利尿过程中，血管加压素(AVP)引起的终末内髓集合管(TIMCD)渗透水通透性增加，使管腔内钙浓度升高(大于或等于5 mM)，高于与尿液中含钙沉淀物形成相关的水平。钙/多阳离子受体蛋白(CARS)使甲状旁腺和肾脏粗大的Henle升支的细胞能够感知并对血清钙的变化做出反应。我们现在报告在大鼠肾脏TIMCD中存在顶端CAR，当腔内钙升高时，该CAR特异性地降低AVP诱导的渗透水的通透性。纯化的tIMCD根尖膜内涵体含有AVP诱导的水通道、水通道蛋白2和CAR。此外，含有水通道蛋白2的内涵体还具有与CARS相互作用的刺激性(G(αq)/G(α11))和抑制(G(αi1，2和3))GTP结合蛋白，以及两种特定的蛋白激酶C亚型(Delta和Zeta)。总之，这些数据为连接钙和水代谢的独特的tIMCD顶膜信号机制提供了支持。这一机制的异常可能在肾结石形成的发病机制中发挥作用。
During antidiuresis, increases in vasopressin (AVP)-elicited osmotic water permeability in the terminal inner medullary collecting duct (tIMCD) raise luminal calcium concentrations to levels (greater than or equal to 5 mM) above those associated with the formation of calcium-containing precipitates in the urine. Calcium/polycation receptor proteins (CaRs) enable cells in the parathyroid gland and kidney thick ascending limb of Henle to sense and respond to alterations in serum calcium. We now report the presence of an apical CaR in rat kidney tIMCD that specifically reduces AVP-elicited osmotic water permeability when luminal calcium rises. Purified tIMCD apical membrane endosomes contain both the AVP-elicited water channel, aquaporin 2, and a CaR. In addition, aquaporin 2-containing endosomes also possess stimulatory (G(alpha q)/G(alpha 11)) and inhibitory (G(alpha i1, 2, and 3)) GTP binding proteins reported previously to interact with CaRs as well as two specific isoforms (delta and zeta) of protein kinase C.Immunocytochemistry using anti-CaR antiserum reveals the presence of CaR protein in both rat and human collecting ducts. Together, these data provide support for a unique tIMCD apical membrane signaling mechanism linking calcium and water metabolism. Abnormalities in this mechanism could potentially play a role in the pathogenesis of renal stone formation.