Aldosterone Requires Vasopressin V1a Receptors on Intercalated Cells to Mediate Acid-Base Homeostasis
Aldosterone Requires Vasopressin V1a Receptors on Intercalated Cells to Mediate Acid-Base Homeostasis
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DOI：
10.1681/asn.2010050468
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发表时间：
2011-04-01
影响因子：
13.6
通讯作者：
Nonoguchi, Hiroshi
中科院分区：
文献类型：
--
作者：
Izumi, Yuichiro;Hori, Kahori;Nonoguchi, Hiroshi
醛固酮和腔内加压素都可能有助于维持酸碱平衡，但这些激素之间的功能关系尚不清楚。管腔加压素的作用可能是由于它与集管内插层细胞的管腔膜上的Via受体相互作用。在这里，我们发现缺乏Via受体的小鼠表现出4型肾小管酸中毒。矿化皮质激素激动剂氟化可的松通过增加Rhcg和h - k - atp酶的表达以及降低h - atp酶的表达来恢复尿铵的排泄，从而改善酸中毒。在表达矿化皮质激素和Via受体而非V2受体的转基因大鼠建立的插层细胞细胞系中，敲低Via受体基因消除了醛固酮对h - k - atp酶、Rhcg和h - atp酶表达的影响。这些数据表明，嵌入细胞中抗利尿激素Via受体的缺陷可导致4型肾小管酸中毒，醛固酮对肾小管的作用取决于嵌入细胞中Via受体的功能。
Both aldosterone and luminal vasopressin may contribute to the maintenance of acid-base homeostasis, but the functional relationship between these hormones is not well understood. The effects of luminal vasopressin likely result from its interaction with Via receptors on the luminal membranes of intercalated cells in the collecting duct. Here, we found that mice lacking the Via receptor exhibit type 4 renal tubular acidosis. The administration of the mineralocorticoid agonist fludrocortisone ameliorated the acidosis by restoring excretion of urinary ammonium via increased expression of Rhcg and H-K-ATPase and decreased expression of H-ATPase. In a cell line of intercalated cells established from transgenic rats expressing the mineralocorticoid and Via receptors, but not V2 receptors, knockdown of the Via receptor gene abrogated the effects of aldosterone on H-K-ATPase, Rhcg, and H-ATPase expression. These data suggest that defects in the vasopressin Via receptor in intercalated cells can cause type 4 renal tubular acidosis and that the tubular effects of aldosterone depend on a functional Via receptor in the intercalated cells.