Downregulation of the V2 vasopressin receptor in dehydration: mechanisms and role of renal prostaglandin synthesis
Downregulation of the V2 vasopressin receptor in dehydration: mechanisms and role of renal prostaglandin synthesis
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DOI：
10.1152/ajprenal.00154.2006
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发表时间：
2007-04-01
影响因子：
4.2
通讯作者：
Nonoguchi, Hiroshi
中科院分区：
文献类型：
--
作者：
Machida, Kenji;Wakamatsu, Shiho;Nonoguchi, Hiroshi
抗利尿激素-水通道蛋白2系统在脱水时尿浓度中起关键作用。与水通道蛋白2的上调相反，抗利尿激素V2受体在脱水时的下调是已知的。我们利用逆转录竞争性聚合酶链反应（RT-competitive PCR）和Western blot分析研究了脱水过程中这种下调的机制。微解剖的内髓收集管（IMCDs）在高渗培养基中或加压素刺激V2受体mRNA和蛋白表达，表明脱水诱导的肾髓质高渗透压和血浆精氨酸加压素（AVP）浓度升高应上调V2受体。脱水过程中可能存在抑制V2受体的因子。已知前列腺素E-2 （PGE(2)）可抑制avp诱导的cAMP产生，并在脱水时增加cAMP的产生。PGE2轻微刺激体外IMCD中V2受体mRNA的表达。然而，在10(-9)M抗利尿激素存在下，PGE2抑制IMCD中V2受体mRNA的表达。吲哚美辛阻断脱水大鼠PGE2合成后，24-48 h后V2受体蛋白表达增加，早期V2受体mRNA表达增加。综上所述，这些数据表明肾髓质PGE2的产生增加在脱水时V2受体的下调中起关键作用。
The vasopressin-aquaporin 2 system plays a key role in urine concentration in dehydration. In contrast to the upregulation of aquaporin 2, the downregulation of the vasopressin V2 receptor in dehydration is known. We investigated the mechanisms of this downregulation in dehydration using reverse transcription-competitive polymerase chain reaction (RT-competitive PCR) and Western blot analysis. The incubation of microdissected inner medullary collecting ducts (IMCDs) in a hypertonic medium or with vasopressin stimulated V2 receptor mRNA and protein expression, showing that dehydration-induced hyperosmolality in renal medulla and increased plasma arginine vasopressin (AVP) concentration should upregulate V2 receptor. The presence of inhibitory factors on the V2 receptor in dehydration was suggested. Prostaglandin E-2 (PGE(2)) is known to inhibit AVP-induced cAMP production and to increase production in dehydration. PGE2 slightly stimulated V2 receptor mRNA expression in IMCD in vitro. However, PGE2 inhibited V2 receptor mRNA expression in IMCD in the presence of 10(-9) M vasopressin. The blockade of PGE2 synthesis by indomethacin in dehydrated rats increased V2 receptor protein expression after 24-48 h with an early increase in V2 receptor mRNA expression. In summary, these data suggest that increased production of PGE2 in renal medulla plays a key role in the downregulation of V2 receptor in dehydration.