Chronic dDAVP infusion in rats decreases the expression of P2Y2 receptor in inner medulla and P2Y2 receptor-mediated PGE2 release by IMCD.
Chronic dDAVP infusion in rats decreases the expression of P2Y2 receptor in inner medulla and P2Y2 receptor-mediated PGE2 release by IMCD.
复制标题
DOI：
10.1152/ajprenal.00177.2005
复制
发表时间：
2005-10
期刊：
影响因子：
--
通讯作者：
Rujia Sun;R. L. Miller;Andrew C. Hemmert;Ping Zhang;Huihui Shi;Raoul D. Nelson;B. Kishore
中科院分区：
文献类型：
--
作者：
Rujia Sun;R. L. Miller;Andrew C. Hemmert;Ping Zhang;Huihui Shi;Raoul D. Nelson;B. Kishore
激活大鼠内髓集合管中的P2Y2受体(P2Y2-R)可降低AVP诱导的水流量并释放PGE(2)。我们观察到，脱水使大鼠内髓(IM)中P2Y2受体的表达减少，并通过IMCD释放由P2Y2-R介导的PGE(2)。由于循环血管加压素(AVP)水平在脱水状态下升高，我们研究了慢性输注去氨加压素(DDAVP)是否对P2Y2-R的表达和活性有类似的影响。各组大鼠分别经渗透压微泵注入生理盐水或DDAVP(5或20 ng/h，sc，5或6天)并安乐死。测定尿量、渗透压和前列腺素E(2)代谢物含量。用实时定量RT-PCR和免疫印迹法检测IM中AQP2、P2Y2和V2-RmRNA和/或蛋白的表达。以ATPGammaS为配体，检测新制备的IMCD对P2Y2-R介导的PGE(2)释放的影响。慢性DDAVP输注导致IM患者尿量减少，AQP2蛋白丰度明显增加。相反，以5或20 ng/h的速度输注DDAVP可显著降低P2Y2-R蛋白丰度(约为生理盐水组的40%)。同时，P2Y2-R与AQP2-或V2-RmRNA的相对表达显著降低。此外，注射20 ng/h DDAVP的大鼠IMCD释放的P2Y2-R介导的PGE(2)显著减少，而不是5 ng/h。然而，尿PGE(2)代谢产物排泄量不随DDAVP的注入而改变。综上所述，慢性DDAVP输注降低了IM中P2Y2-R的表达和活性。这可能是由于DDAVP或DDAVP诱导的髓质紧张性增加的直接作用。
Activation of P2Y2 receptor (P2Y2-R) in inner medullary collecting duct (IMCD) of rat decreases AVP-induced water flow and releases PGE(2). We observed that dehydration of rats decreases the expression of P2Y2 receptor in inner medulla (IM) and P2Y2-R-mediated PGE(2) release by IMCD. Because circulating vasopressin (AVP) levels are increased in dehydrated condition, we examined whether chronic infusion of desmopressin (dDAVP) has a similar effect on the expression and activity of P2Y2-R. Groups of rats were infused with saline or dDAVP (5 or 20 ng/h sc, 5 or 6 days) via osmotic minipumps and euthanized. Urine volume, osmolality, and PGE(2) metabolite content were determined. AQP2- and P2Y2- and V2-R mRNA and/or protein in IM were quantified by real-time RT-PCR and immunoblotting, respectively. P2Y2-R-mediated PGE(2) release by freshly prepared IMCD was assayed using ATPgammaS as a ligand. Chronic dDAVP infusion resulted in low-output of concentrated urine and significantly increased the AQP2 protein abundance in IM. On the contrary, dDAVP infusion at 5 or 20 ng/h significantly decreased P2Y2-R protein abundance (approximately 40% of saline-treated group). In parallel, the relative expression of P2Y2-R vs. AQP2- or V2-R mRNA was significantly decreased. Furthermore, the P2Y2-R-mediated PGE(2) release by IMCD was significantly decreased in rats infused 20 ng/h but not 5 ng/h of dDAVP. Urinary PGE(2) metabolite excretion, however, did not change with dDAVP infusion. In conclusion, chronic dDAVP infusion decreases the expression and activity of P2Y2-R in IM. This may be due to a direct effect of dDAVP or dDAVP-induced increase in medullary tonicity.