Guan Y, Zhang Y, Breyer R M, Fowler B, Davis L, Hébert R L, Breyer M D
Division of Nephrology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA.
J Clin Invest. 1998 Jul 1;102(1):194-201. doi: 10.1172/JCI2872.
PGE2 exerts potent diuretic and natriuretic effects on the kidney. This action is mediated in part by direct inhibition of collecting duct Na+ absorption via a Ca++-coupled mechanism. These studies examine the role the Ca++-coupled PGE-E EP1 receptor plays in mediating these effects of PGE2 on Na+ transport. Rabbit EP1 receptor cDNA was amplified from rabbit kidney RNA. Nuclease protection assays demonstrated highest expression of EP1 mRNA in kidney, followed by stomach, adrenal, and ileum. In situ hybridization, demonstrated renal expression of EP1 mRNA was exclusively over the collecting duct. In fura-2-loaded microperfused rabbit cortical collecting duct, EP1 active PGE analogs were 10-1, 000-fold more potent in raising intracellular Ca++ than EP2, EP3, or EP4-selective compounds. Two different EP1 antagonists, AH6809 and SC19220, completely blocked the PGE2-stimulated intracellular calcium increase. AH6809 also completely blocked the inhibitory effect of PGE2 on Na+ absorption in microperfused rabbit cortical collecting ducts. These studies suggest that EP1 receptor activation mediates PGE2-dependent inhibition of Na+ absorption in the collecting duct, thereby contributing to its natriuretic effects.
前列腺素E2（PGE2）对肾脏具有强大的利尿和排钠作用。这一作用部分是通过一种钙偶联机制直接抑制集合管对钠离子的重吸收来介导的。这些研究探讨了钙偶联的前列腺素E（PGE）-EP1受体在介导PGE2对钠离子转运的这些作用中所起的作用。兔EP1受体cDNA是从兔肾RNA中扩增得到的。核酸酶保护试验表明，EP1 mRNA在肾脏中的表达最高，其次是胃、肾上腺和回肠。原位杂交显示，EP1 mRNA在肾脏中的表达仅在集合管中。在装载了fura-2的微灌流兔皮质集合管中，EP1活性PGE类似物在升高细胞内钙离子方面的效力比EP2、EP3或EP4选择性化合物强10至1000倍。两种不同的EP1拮抗剂AH6809和SC19220完全阻断了PGE2刺激引起的细胞内钙升高。AH6809也完全阻断了PGE2对微灌流兔皮质集合管中钠离子重吸收的抑制作用。这些研究表明，EP1受体激活介导了PGE2依赖性的集合管钠离子重吸收抑制，从而促成其排钠作用。
