Renal vasculature reactivity to agonist of P2X7 receptor is increased in streptozotocin-induced diabetes
Renal vasculature reactivity to agonist of P2X7 receptor is increased in streptozotocin-induced diabetes
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DOI：
10.1016/j.pharep.2015.06.140
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发表时间：
2016-01-01
影响因子：
4.4
通讯作者：
Szczepanska-Konkel, Miroslawa
中科院分区：
文献类型：
--
作者：
Kreft, Ewelina;Kowalski, Robert;Szczepanska-Konkel, Miroslawa
背景：糖尿病肾病的特点是肾微血管功能障碍。作为嘌呤能系统一部分的 P2X7 受体可能参与了这一过程。本研究的目的是探讨糖尿病大鼠P2X7受体介导的肾微血管反应和细胞外腺嘌呤核苷酸的肾代谢。方法：以链脲佐菌素诱导的糖尿病Wistar大鼠为研究对象。根据皮质血流量（CBF）、肾小球滤过率（GFR）和肾小球菊粉间隙（GIS）的变化监测血管对P2X7受体激动剂BzATP的反应。通过微透析技术探测肾间质液（RIF）并测量 ATP 和腺苷的浓度。测量肾膜上 NTDPase 和 5'-核苷酸酶的活性。结果：糖尿病肾脏的特点是 ATP RIF 降低和腺苷 RIF 浓度增加，同时 NTDPase 和 5'-核苷酸酶活性增强。 BzATP 诱导糖尿病大鼠更显着的 CBF 增加和 GFR 和 GIS 降低。这些作用被P2X7受体拮抗剂A438079消除。结论：P2X7受体反应性增加可能参与糖尿病肾病的发病机制。 (c) 2015 年波兰科学院药理学研究所。由爱思唯尔公司出版。 z o.o.版权所有。
Background: Diabetic nephropathy is characterized by the dysfunction of renal microvasculature. The involvement of the P2X7 receptor, being a part of the purinergic system, is presumable in this process. The aim of our study was to investigate the P2X7 receptor-mediated renal microvasculature response and renal metabolism of extracellular adenine nucleotides in diabetic rats.Methods: Study was performed on streptozotocin-induced diabetic Wistar rats. The vascular response to BzATP, an agonist of the P2X7 receptor, was monitored based on the changes of cortical blood flow (CBF), glomerular filtration rate (GFR) and glomerular inulin space (GIS). The renal interstitial fluid (RIF) was probed by microdialysis technique and concentrations of ATP and adenosine were measured. Activity on NTDPase and 5'-nucleotidases was measured on renal membranes.Results: Diabetic kidneys were characterized by decreased ATP RIF and increased adenosine RIF concentrations with accompanied enhancement of NTDPase and 5'-nucleotidase activities. BzATP induced a more pronounced increase of CBF and decrease of GFR and GIS in diabetes rats. These effects were abolished by A438079, an antagonist of the P2X7 receptor.Conclusions: It is possible that increased P2X7 receptor reactivity may be involved in the pathogenesis of diabetic nephropathy. (c) 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.