Potential involvement of P2Y2 receptor in diuresis of postobstructive uropathy in rats.
Potential involvement of P2Y2 receptor in diuresis of postobstructive uropathy in rats.
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DOI：
10.1152/ajprenal.00382.2009
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发表时间：
2010-03
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影响因子：
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通讯作者：
Yue Zhang;D. Kohan;R. Nelson;N. Carlson;B. Kishore
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作者：
Yue Zhang;D. Kohan;R. Nelson;N. Carlson;B. Kishore
梗阻性尿路病变 (POU) 中髓质集合管 (mCD) 的 AVP 抵抗归因于 PGE2 产生的增加。 P2Y2 受体激活导致 mCD 产生 PGE2。我们假设 P2Y2 受体表达和/或活性增加可能有助于 POU 的利尿作用。 Sprague-Dawley 大鼠双侧输尿管梗阻 24 小时，然后释放（BUO/R，n = 17）或假手术（SHM/O，n = 15），并在 1 周或 12 天后安乐死。与 SHM/O 大鼠相比，BUO/R 大鼠出现明显的多饮、多尿、尿浓缩缺陷，尿 PGE2 增加，内髓质水通道蛋白 2 蛋白丰度降低。 BUO/R后，P2Y2和P2Y6受体的相对mRNA表达分别增加2.7倍和4.9倍，而P2Y1或P2Y4受体的mRNA表达没有显着变化。这与 BUO/R 大鼠中 P2Y2 受体的蛋白质丰度显着高于 SHM/O 大鼠 3.5 倍相关。当新鲜分离的 mCD 组分受到不同类型的核苷酸（ATPgammaS、ADP、UTP 或 UDP）攻击时，BUO/R 和 SHM/O 大鼠仅对 ATPgammaS 和 UTP 做出反应并释放 PGE2，这与 P2Y2 受体的参与一致，但与 P2Y6 受体的参与无关。 BUO/R 大鼠中 ATPgammaS 或 UTP 刺激的 PGE2 增加（分别是载体对照的 3.20 倍和 2.28 倍）比 SHM/O 大鼠（分别是载体对照的 1.68 倍和 1.30 倍）高得多。此外，与 SHM/O 大鼠相比，BUO/R 大鼠髓内部的前列腺素类 EP1 和 EP3 受体的相对 mRNA 表达分别显着增加 2.4 倍和 2.1 倍。总而言之，这些数据表明 POU 中 mCD 产生的 PGE2 增加可能是由于 P2Y2 受体表达和活性增加所致。 POU 中 EP1 和 EP3 受体 mRNA 表达的增加也可能有助于增强 mCD 中 PGE2 诱导的信号传导。
AVP resistance of the medullary collecting duct (mCD) in postobstructive uropathy (POU) has been attributed to increased production of PGE2. P2Y2 receptor activation causes production of PGE2 by the mCD. We hypothesize that increased P2Y2 receptor expression and/or activity may contribute to the diuresis of POU. Sprague-Dawley rats were subjected to bilateral ureteral obstruction for 24 h followed by release (BUO/R, n = 17) or sham operation (SHM/O, n = 15) and euthanized after 1 wk or 12 days. BUO/R rats developed significant polydipsia, polyuria, urinary concentration defect, and increased urinary PGE2 and decreased aquaporin-2 protein abundance in the inner medulla compared with SHM/O rats. After BUO/R, the relative mRNA expression of P2Y2 and P2Y6 receptors was increased by 2.7- and 4.9-fold, respectively, without significant changes in mRNA expression of P2Y1 or P2Y4 receptor. This was associated with a significant 3.5-fold higher protein abundance of the P2Y2 receptor in BUO/R than SHM/O rats. When freshly isolated mCD fractions were challenged with different types of nucleotides (ATPgammaS, ADP, UTP, or UDP), BUO/R and SHM/O rats responded to only ATPgammaS and UTP and released PGE2, consistent with involvement of the P2Y2, but not P2Y6, receptor. ATPgammaS- or UTP-stimulated increases in PGE2 were much higher in BUO/R (3.20- and 2.28-fold, respectively, vs. vehicle controls) than SHM/O (1.68- and 1.30-fold, respectively, vs. vehicle controls) rats. In addition, there were significant 2.4- and 2.1-fold increases in relative mRNA expression of prostanoid EP1 and EP3 receptors, respectively, in the inner medulla of BUO/R vs. SHM/O rats. Taken together, these data suggest that increased production of PGE2 by the mCD in POU may be due to increased expression and activity of the P2Y2 receptor. Increased mRNA expression of EP1 and EP3 receptors in POU may also help accentuate PGE2-induced signaling in the mCD.