The intercalated cells of the mouse kidney OMCDis are the target of the vasopressin V1a receptor axis for urinary acidification
The intercalated cells of the mouse kidney OMCDis are the target of the vasopressin V1a receptor axis for urinary acidification
复制标题
小鼠肾脏 OMCDis 的嵌入细胞是尿液酸化的加压素 V1a 受体轴的目标
DOI：
10.1007/s10157-013-0783-y
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发表时间：
2013
期刊：
影响因子：
2.3
通讯作者：
Kawahara K
中科院分区：
文献类型：
--
作者：
Yasuoka Y;Kobayashi M;Sato Y;Zhou M;Abe H;Okamoto H;Nonoguchi H;Tanoue A;Kawahara K
背景加压素V1 a受体（V1 aR）基因敲除小鼠存在酸碱失衡，但V1 aR信号转导的靶细胞尚未确定，导致尿酸化。方法采用定量原位杂交技术和抗AQP 3抗体双染技术，研究了V1 aR mRNA在小鼠肾单位的轴向分布和酸中毒诱导的V1 aR mRNA沿着表达。我们还调查了酸中毒诱导的形态学变化的肾小管细胞从野生型和V1 aR-null（V1 aR-/-）mice.ResultsIn正常条件下，V1 aR mRNA中度表达在髓质厚升支（MTAL）和高度表达在闰细胞（IC）整个集合管（CD）。然而，在近端小管、Henle袢的细肢和CD的主细胞中未观察到表达。重要的是，当小鼠用NH_4Cl（0.28 mol/L）处理6d时，在外髓内条的TAL和CD的IC（分别为MTALis和OMCDis的IC）中V1 aR mRNA均显著上调。在V1 aR −/−小鼠中完全减弱的酸中毒诱导的肥大仅在OMCDis的IC中观察到（P< 0.005）。另外，V1 aR −/−小鼠经NH 4Cl处理后，第3天和第6天尿氨排泄量（NH3/NH 4+）显著减少（P <0. 05）。结论OMCDisIC可能是加压素V1 aR轴刺激的靶细胞，参与了代谢性酸中毒时的尿酸化。
BackgroundVasopressin V1a receptor (V1aR) null mice have insufficient acid–base balance, but the target cell for V1aR signaling which results in the urinary acidification has not been identified.MethodsBy using a quantitative in situ hybridization technique and a double-staining technique with an anti-AQP3 antibody in mice, we investigated the axial distribution and acidosis-induced expression of V1aR mRNA along the nephron. We also investigated the acidosis-induced morphological change in the tubule cells from wild-type and V1aR-null (V1aR−/−) mice.ResultsIn the normal condition, V1aR mRNA was moderately expressed in the medullary thick ascending limb (MTAL) and highly expressed in the intercalated cell (IC) throughout the collecting duct (CD). However, no expression was observed in the proximal tubule, thin limbs of Henle’s loop, and the principal cell of the CD. Importantly, V1aR mRNA was upregulated significantly both in the TAL and the IC of the CD in the inner stripe of the outer medulla (MTALisand IC of OMCDis, respectively) when mice were treated with NH4Cl (0.28 mol/L) for 6 days. Acidosis-induced hypertrophy, which was completely attenuated in V1aR−/−mice, was observed only in the IC of OMCDis(P< 0.005). In addition, urinary excretion of ammonia (NH3/NH4+) was significantly decreased on day 3 (P< 0.05) and day 6 (P< 0.005) in the V1aR−/−mice treated with NH4Cl.ConclusionIn conclusion, the IC of OMCDismay be the target cell stimulated by the vasopressin V1aR axis and contribute to urinary acidification, at least during metabolic acidosis.