Regulation of renal function by prostaglandin E receptors
Regulation of renal function by prostaglandin E receptors
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DOI：
10.1046/j.1523-1755.1998.06718.x
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发表时间：
1998-09-01
影响因子：
19.6
通讯作者：
Breyer, RM
中科院分区：
文献类型：
--
作者：
Breyer, MD;Zhang, YH;Breyer, RM
前列腺素E-2是沿肾单位产生的花生四烯酸代谢的主要环氧合酶产物。它与四个不同的G蛋白偶联的E-前列腺素受体相互作用，命名为EP1-EP4。已经绘制了每个受体在肾内的分布图，并检查了受体激活的后果。EP3受体在髓质粗大的升支(MTAL)和集合管(CD)高表达。EP3受体的激活通过G(I)抑制cAMP的生成，从而抑制血管加压素刺激的CD中的水重吸收。EP3受体的激活也可能参与了PGE(2)介导的抑制mTAL对盐吸收的作用。EP1受体与升高的细胞内钙离子偶联。EP1mRNA的表达仅限于CD，受体激活抑制Na+的吸收。PGE(2)还可增加皮质粗大升肢和CD中cAMP的生成；这可能是由于EP4受体激活所致。CD中EP4基因表达较强，而EP2基因表达较弱。EP4受体似乎在管腔和基底膜上都有表达。EP4受体的激活也可能参与肾小球旁结构对肾素释放的调节。肾脏EP受体激活对盐和水平衡的影响可能取决于这些受体在肾脏中的相对表达。
Prostaglandin E-2 is the major cyclooxygenase product of arachidonic acid metabolism produced along the nephron. This autacoid interacts with four distinct, G-protein-coupled E-prostanoid receptors designated EP1-EP4. The intrarenal distribution of each receptor has been mapped and the consequences of receptor activation examined. EP3 receptor mRNA is expressed highly in the medullary thick ascending limb (mTAL) and collecting duct (CD). EP3 receptor activation inhibits cAMP generation via G(i), thus inhibiting vasopressin-stimulated water reabsorption in the CD. EP3 receptor activation also may contribute to PGE(2)-mediated inhibition of NaCl absorption in the mTAL. The EP1 receptor is coupled to increased cell [Ca2+]. EP1 mRNA expression is restricted to the CD, and receptor activation inhibits Na+ absorption. PGE(2) also increases cAMP generation in the cortical thick ascending limb and CD; this may be due to EP4 receptor activation. EP4 mRNA is readily detected in the CD with little detectable EP2 expression. The EP4 receptor appears to be expressed both on luminal and basolateral membranes. EP4 receptor activation also may contribute to the regulation of renin release by the juxtaglomerular apparatus. The consequences of renal EP-receptor activation for salt and water balance may be determined by the relative renal expression of each of these receptors.