P2Y2 receptor-mediated release of prostaglandin E2 by IMCD is altered in hydrated and dehydrated rats: relevance to AVP-independent regulation of IMCD function.
P2Y2 receptor-mediated release of prostaglandin E2 by IMCD is altered in hydrated and dehydrated rats: relevance to AVP-independent regulation of IMCD function.
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DOI：
10.1152/ajprenal.00050.2005
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发表时间：
2005-09
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影响因子：
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通讯作者：
Rujia Sun;N. Carlson;A. Hemmert;B. Kishore
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文献类型：
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作者：
Rujia Sun;N. Carlson;A. Hemmert;B. Kishore
循环加压素水平在水合和脱水条件下变化，从而控制内髓集合管（IMCD）的渗透水渗透性（P（f））。前列腺素E_2（PGE_2）拮抗加压素诱导的IMCD的P（f）。先前，我们发现IMCD中P2 Y2受体（P2 Y2-R）的激活导致PGE 2的产生和释放，并且与脱水大鼠相比，在水合大鼠的内髓质中P2 Y2-R mRNA和蛋白显著升高。因此，我们研究了P2 Y2-R在水合和脱水状态下的表达改变是否与IMCD中P2 Y2-R介导的PGE 2释放的相应变化相关。通过提供蔗糖水作为唯一饮用流体使大鼠水合或通过缺水2天使大鼠脱水。这分别导致水合和脱水大鼠的高输出-低渗透压和低输出-高渗透压尿液。在水合大鼠中，通过评估尿PGE 2代谢产物间接测量的肾小管液PGE 2显著增加。用P2 Y2-R激动剂（ATP γ S）刺激新鲜分离的IMCD制剂，显示与正常大鼠相比，水合大鼠中PGE 2的释放显著增加。这些反应在脱水大鼠制备的IMCD中减弱。P2 Y2-R介导的大鼠IMCD中PGE 2的释放主要由环氧合酶（考克斯）-1介导，因为考克斯-1特异性抑制剂水杨酸戊酰酯完全阻断了该释放。考克斯-2特异性抑制剂N5398仅具有适度且不显著的抑制作用。总之，嘌呤能-前列腺素类相互作用的敏感性增加，在IMCD的水合大鼠可能代表一种新的加压素独立的IMCD功能的调节机制。
Circulating vasopressin levels change in hydrated and dehydrated conditions and thus control osmotic water permeability (P(f)) of the inner medullary collecting duct (IMCD). Prostaglandin E2 (PGE2) antagonizes vasopressin-induced P(f) of IMCD. Previously, we showed that activation of P2Y2 receptor (P2Y2-R) in IMCD results in production and release of PGE2, and P2Y2-R mRNA and protein are significantly elevated in inner medullas of hydrated rats compared with dehydrated rats. Therefore, we examined whether the altered expression of P2Y2-R in hydrated and dehydrated states is associated with corresponding changes in P2Y2-R-mediated PGE2 release by the IMCD. Rats were hydrated by providing sucrose water as the sole drinking fluid or dehydrated by water deprivation for 2 days. This resulted in high output-low osmolality and low output-high osmolality urines in hydrated and dehydrated rats, respectively. In hydrated rats, there was a significant increase in tubular fluid PGE2, measured indirectly by assessing the urinary PGE2 metabolite. Stimulation of freshly isolated IMCD preparations in vitro with P2Y2-R agonist (ATPgammaS) showed a marked increase in the release of PGE2 in hydrated rats compared with normal rats. These responses were blunted in the IMCD prepared from dehydrated rats. The P2Y2-R-mediated PGE2 release in the IMCD of hydrated rats was mediated largely by cyclooxygenase (COX)-1 as COX-1-specific inhibitor valeroyl salicylate completely blocked the release. The COX-2-specific inhibitor N5398 had only a modest and insignificant inhibitory effect. In conclusion, the increased sensitivity of purinergic-prostanoid interaction seen in the IMCD of hydrated rats may represent a novel vasopressin-independent regulatory mechanism of IMCD function.