Galphaq-dependent signaling cascades stimulate water-seeking behavior.
Galphaq-dependent signaling cascades stimulate water-seeking behavior.
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Galphaq 依赖性信号级联刺激寻水行为。
DOI：
10.1152/ajprenal.00401.2005
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Spurney,RobertF
中科院分区：
文献类型：
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作者：
Wang,Liming;Flannery,PatrickJ;Athirakul,Krairerk;Dunn,StephenR;Kourany,WissamM;Spurney,RobertF
我们使用小鼠nephrin启动子在小鼠中表达组成型活性的Gαq [Gαq（Q>L）]转基因。如前所述，转基因在肾脏、胰腺和脑中表达，肾脏表型的特征是蛋白尿和肾单位质量减少。进一步的研究揭示了第二个表型的特点是多尿和烦渴。多尿表型不是由糖代谢异常或高钙血症引起的，而是伴随着尿浓缩能力降低。其他研究发现：1）限水与转基因（TG）小鼠血清加压素水平的适当增加有关;2）给予脱氨基-d-精氨酸加压素（DDAVP）不能纠正尿浓缩缺陷; 3）TG和非TG小鼠的乳头长度相似。为了在分子水平上研究肾脏对DDAVP的反应，我们监测了小鼠肾脏水通道蛋白2（AQP 2）和血管加压素V2受体（V2 R）的mRNA水平。与加压素的已知作用一致，DDAVP给药导致TG和非TG动物中V2 R mRNA水平降低和AQP 2 mRNA水平升高，表明TG小鼠对DDAVP有适当的肾脏反应。为了确定尿浓缩异常是否是原发性烦渴的结果，将TG小鼠的水摄入量限制为非TG动物的摄入量。5天后，TG小鼠和非TG同窝对照小鼠的尿浓缩能力相似。这些数据与脑中Gαq（Q>L）转基因表达诱导TG小鼠原发性烦渴的观点一致。
We used the mouse nephrin promoter to express a constitutively active Gαq [Gαq(Q>L)] transgene in mice. As previously reported, the transgene was expressed in kidney, pancreas, and brain, and the kidney phenotype was characterized by albuminuria and reduced nephron mass. Additional studies revealed a second phenotype characterized by polyuria and polydipsia. The polyuric phenotype was not caused by abnormal glucose metabolism or hypercalcemia but was accompanied by reduced urinary concentrating ability. Additional studies found that1) water restriction was associated with an appropriate increase in serum vasopressin levels in transgenic (TG) mice;2) the urinary concentrating defect was not corrected by administration of desamino-d-arginine vasopressin (DDAVP); and3) papillary length was similar in TG and non-TG mice. To examine the renal response to DDAVP at the molecular level, we monitored aquaporin 2 (AQP2) and vasopressin V2 receptor (V2R) mRNA levels in mouse kidney. Consistent with the known effects of vasopressin, administration of DDAVP caused a decrease in V2R mRNA levels and an increase in AQP2 mRNA levels in both TG and non-TG animals, suggesting an appropriate renal response to DDAVP in the TG mice. To determine whether the urine concentrating abnormality was the result of primary polydipsia, water intake by TG mice was restricted to the amount ingested by non-TG animals. After 5 days, urinary concentrating ability was similar in TG mice and non-TG littermate controls. These data are consistent with the notion that expression of the Gαq(Q>L) transgene in the brain induced primary polydipsia in the TG mice.