Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting duct
Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting duct
复制标题
DOI：
10.1152/ajprenal.00049.2006
复制
发表时间：
2007-01-01
影响因子：
4.2
通讯作者：
Breyer, Matthew D.
中科院分区：
文献类型：
--
作者：
Carmosino, Monica;Brooks, Heddwen L.;Breyer, Matthew D.
血管加压素和血管加压素拮抗剂在小鼠疾病模型和临床医学中的用途正在扩大。为了进一步了解V1 a和V2血管加压素受体在人类和小鼠肾脏中的生理作用，通过原位杂交确定受体mRNA的肾内定位。V2受体mRNA主要在髓质中表达，而V1 a受体mRNA主要在皮质中表达。血管加压素受体mRNA的节段性定位采用原位杂交和免疫组织化学方法确定节段特异性标记物，包括水通道蛋白2、双花扁豆凝集素、上皮Na通道、Tamm-Horsfall糖蛋白和噻嗪敏感性Na+-Cl-协同转运蛋白。值得注意的是，V1 a受体表达仅在小鼠和人肾脏髓质集合管的V-ATP酶/阴离子交换剂-1-标记的α-闰细胞中表达。在皮质集合管中，V1 a mRNA分布更广，在主细胞和闰细胞中均检测到。在小鼠和人肾脏中，V2受体mRNA沿集合管沿着弥散表达，在髓质中表达水平较高。这些结果表明V1 a和V2加压素受体沿着人和小鼠集合管的异质轴向表达。V1 a受体mRNA在闰细胞中的限制性表达表明该受体在酸碱平衡中的作用。这些发现进一步表明AVP通过皮质与髓质中的V1 a和V2受体对肾转运功能进行不同的调节。
Vasopressin and vasopressin antagonists are finding expanded use in mouse models of disease and in clinical medicine. To provide further insight into the physiological role of V1a and V2 vasopressin receptors in the human and mouse kidney, intrarenal localization of the receptors mRNA was determined by in situ hybridization. V2-receptor mRNA was predominantly expressed in the medulla, whereas mRNA for V1a receptors predominated in the cortex. The segmental localization of vasopressin-receptor mRNAs was determined using simultaneous in situ hybridization and immunohistochemistry for segment-specific markers, including aquaporin-2, Dolichos biflorus agglutinin, epithelial Na channels, Tamm Horsfall glycoprotein, and thiazide-sensitive Na+-Cl- cotransporter. Notably, V1a receptor expression was exclusively expressed in V-ATPase/anion exchanger-1-labeled alpha-intercalated cells of the medullary collecting duct in both mouse and human kidney. In cortical collecting ducts, V1a mRNA was more widespread and detected in both principal and intercalated cells. V2-receptor mRNA is diffusely expressed along the collecting ducts in both mouse and human kidney, with higher expression levels in the medulla. These results demonstrate heterogenous axial expression of both V1a and V2 vasopressin receptors along the human and mouse collecting duct. The restricted expression of V1a-receptor mRNA in intercalated cells suggests a role for this receptor in acid-base balance. These findings further suggest distinct regulation of renal transport function by AVP through V1a and V2 receptors in the cortex vs. the medulla.